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Disclosures: CNS Productions, Dominion Diagnostics, J. of Psychoactive Drugs Disclaimers: Dynamic and vitally important discoveries are being made almost every month in the science of addiction. For some, each innovation is thought to be the long-sought solution and cure of this catastrophic medical disorder and they are tremendously disappointed when the implementation of the discovery to treatment and prevention of addiction only yields a small or modest improvement in outcomes. For Others, the explosive growth in the science and technical understanding of addiction is so rapid and overwhelming that it is hard to understand, keep up with, and actually discouraging. Addiction is and has always been a multi-faceted disorder of biology, environment, emotions and spirituality. Baffling, Cunning, and Powerful…Bill W. 1962. Some add Brutal to that list. Each new discovery only helps to validate the established interventions that have been practiced proven to engage and hold addicts into the life-long process of recovery. Or Disclaimers: Lens, Ted and Mabel or Dr. Bob Stories Acknowledgement: Managing and especially initiating recovery is very difficult, “it’s easy, all you have to do is change everything about you and everything you do”

Bottom bullet is less than 50% adherence to treatment or abstinence to their drug of choice 1 year post treatment; 40% adherent to medications and 30% continue to life style changes (low sodium) 1 year post hypertensive treatment. From: Dr. Adam Rzetelny PhD. Director of Clinical Affairs of Millennium Labs at the ORPRN Conference in Salem OR. 4/12/14

Reason is neurochemical and neurofunctional similarities of drug use and impulse control disorders. Internet Gambling also accepted but Internet Gaming, texting, et al., sex (porn) are conditions under further consideration and though caffeine addiction and withdrawal symptoms specified it is also a disorder under further consideration. Hoarding Disorder is a component of OCD in DSM IV, Internet addiction put off for more confirmation, Sexual addiction? Eating Disorders (Anorexia Nervosa, A. Bulemia – purging or exercise, Binge ED, Compulsive Overeating) are their own separate diagnosis section of DSM IV and probably will continue to be so in V though brain imaging research (Nora Volkow) demonstrate its similarity with chemical addictions. Hormonal considerations in eating disorder: An empty stomach releases hormone/enzyme Ghrelin. This causes the hypothalamus to release dopamine to activate the NAc “go switch” resulting in a search for food to survive (cannabinoid CB1 receptors also do this). Fat cells release leptin that then counteracts ghrelin = satiation. Orexin increases dopamine saliency of psychoactive foods (refined carbohydrates) to increase food cravings. DSM-5 also establishes addiction as a spectrum disorder mild, moderate, severe.

Again, Bill Cohen: Addiction is Overactive Go Switch, Damaged Stop Switch, and Lack of Communication between the two switches.

Kevin McCauley correctly expand the mechanism of addiction to consist of five brain functions hijacked to cause the dysfunction of choice in vulnerable individuals: Genetics, Reward Reinforcement Circuitry, Memory of pleasure or survival (glutamate is the chemical of memory formation and of drug seeking or craving), Stress (mechanism of craving, distorts brains ability to recognize pleasure – “Addiction is a stress-induced defect in the midbrain’s ability to properly perceive pleasure”), and frontal cortex (choice). Human altruism is challenged when disability is not readily visible as is acceptance of the disability in those affected. Addiction may be only disorder that requires a “self diagnosis” for acceptance and healing to begin.

Only single celled animals and plants for 3.5 billion years then Cambrian Explosion of multi-cellular plants and animals 500 million years ago. These needed specialized cells to coordinate their multiple cell - neurons evolved Important because addiction starts in in unconscious, instinctive, reactive, unthinking, survival oriented diencephalon and mammalian mesocortex.

This panel focuses on important regions of the limbic system that was shown in purple on the previous slide. The nucleus accumbens is the “center of the universe” for experiencing the reinforcing effects of drugs of abuse, and nearly all drugs of abuse activate the nucleus accumbens The neuronal projection from the VTA to the nucleus accumbens and prefrontal cortex comprises a major component of what is knows as the mesolimbic dopamine system. Dopamine-containing neurons in the VTA project to the NAcc and release dopamine there. This process is thought to produce sensations of pleasure and well-being. The VTA also sends projections to the prefrontal cortex, and dopamine release there also contributes to the reinforcing effects of drugs of abuse. The prefrontal cortex also receives input from other limbic brain regions thought to be involved in drug reinforcement, such as the amygdala, hippocampus, and anterior cingulate. The prefrontal cortex sends glutamatergic projections back to the nucleus accumbens. As such, the prefrontal cortex is a region that could integrate information from a variety of brain areas associated with drug reinforcement, and modulate responses of these brain areas to drug administration. It has been discovered that nearly all drugs of abuse increase nucleus accumbens dopamine, and for years, the prevailing hypothesis was that dopamine was the key neurotransmitter subserving the reinforcing effects of all drugs of abuse. In recent years, however, it has become apparent that dopamine is not the only “reward” neurotransmitter, and that other neurotransmitters play key roles. In support of this, destroying the dopaminergic projection from the VTA to the nucleus accumbens does not alter alcohol intake in animals. Clearly, other neurotransmitters are involved. Opioid peptides have also been shown to play an important role in alcohol intake. The arcuate nucleus of the hypothalamus contains opioid peptides which can be released and can bind to receptors in the nucleus accumbens and VTA. As such, opioid peptides are reward neurotransmitters in much the same way that dopamine is. What happens is that when we satisfy basic needs by finding water, food, or companionship, a signal is sent through a system known as “the reward reinforcement pathway,” particularly the nucleus accumbens, also known as the go switch. This go switch tells us three things. It says that what we did was necessary for survival, it says that we should remember what we did to find the food, or water, or other basic need and it tells us to do it again, and again, and again.

The red arrow shows the mesolimbic dopaminergic reward/reinforcement pathway of the brain. The reward system is the part of the CNS most responsible for addiction. Normally, it signals pleasure when some physical need is met. It also responds when certain psychoactive drugs are taken. This surge, caused by psychoactive drugs, reinforces their use and often triggers an intense craving. It also disables the satiation/stop switch in the prefrontal cortex.

NAs of those vulnerable to addiction activates up to 1000X more from the same amount of cocaine or drug exposure as the brain of Normies or Super Normies. Remember though that this is in the unconscious, automatic, instinctive, unfeeling sub-cortical brain. These are PET scans of a person’s brain on cocaine. The yellow areas are where cocaine is exciting the brain, giving a rush. At 6 to 8 minutes there is maximum involvement in all areas and then it starts to diminish. At 20 to 30 minutes, it has spent its major effects. This progression is similar to the effect the anticipation to gamble has on the brain of a gambler. In that case, two forms of adrenaline and dopamine are released, and it takes 20 to 30 minutes for that adrenaline to be reabsorbed. This means that when a craving pops into our head, we need to do something to let 20 to 30 minutes pass to let the adrenaline be reabsorbed. There dozens of activities that we can use . . . .

Thus normal controls have greater activation (feelings) from the same amount of cocaine in the conscious, aware, feeling brain as compared to the experience of those vulnerable to cocaine addiction. Lower Relative Glucose Metabolism in the Prefrontal Cortex and Anterior Cingulate Gyrus of a Cocaine Abuser Than in a Normal Comparison Subject Drug Addiction and Its Underlying Neurobiological Basis: Neuroimaging Evidence for the Involvement of the Frontal Cortex Rita Z. Goldstein, Ph.D. and Nora D. Volkow, M.D. Am J Psychiatry. Author manuscript; available in PMC 2005 September 13. Published in final edited form as: Am J Psychiatry. 2002 October; 159(10): 1642–1652.

Beta pancreatic cells of diabetic is biologically different from non-diabetics

VTA cells of morphine addict is biologically different in opioid addict than in normies. Nestler Lab, Fishberg Dept. of Neuroscience, Mount Sinai School of Medicine. 1997 http://neuroscience.mssm.edu/NeuroscienceLabs/NestlerLab/research_neuro.php accessed 11/12/11

The red arrow shows the mesolimbic dopaminergic reward/reinforcement pathway of the brain. The reward system is the part of the CNS most responsible for addiction. Normally, it signals pleasure when some physical need is met. It also responds when certain psychoactive drugs are taken. This surge, caused by psychoactive drugs, reinforces their use and often triggers an intense craving. It also disables the satiation/stop switch in the prefrontal cortex.

“Stop Switch” per se is thus right behind the left eye. This is inactive in many addicts perhaps due to early onset drug use that impairs or delays the development of this area of the brain. Takes until age 25 to become hard wired enough to function adequately. Age of first use continues to be best predictor of future addiction problems. (10-12 yo 400-500% greater addiction than 17-18 yo first use and is 19 times greater than those who wait until 25 or older to experiment with an addictive substance. Fasciculus retroflexus and lateral habenula are parts of a cluster of neuron fibers that connect the Stop Switch with the Go Switch to facilitate communication between these two circuitries of the addiction pathway. Some addicts have a fully functional OFC Go Switch but have non-function communication fibers. Excess dopamine cause degeneration of these fibers especially nicotine exposure. Traumatic Brain Injury and Addiction: 9/13/1848 Phineas Gage, a railroad worker, had a 3 feet tamping iron go through his face up through his left eye and then through the top of his head. He lived until 1860 giving science a chance to see what consequences this had. About 20% of those who get a TBI become vulnerable to addiction: Dennis James, Mitzi Jarrett, Shree Shalerae, Carissa Courtnery Toronto, Cananda OFC and addiction: Verdejo-Garcia, A., Bechara, A., Recknor, E. C., Perez-Garcia, M. (2006). Executive dysfunction in substance dependent individuals during drug use and abstinence: An examination of the behavioral, cognitive and emotional correlates of addiction. Journal of the International Neuropsychological Society, 12, 405–415; Paulus, M. P., Hozack, N. E., Zauscher, B. E., Frank, L., Brown, G. G., Braff, D. L., &amp; Schuckit, M. A. (2002). Behavioral and Functional Neuroimaging Evidence for Prefrontal Dysfunction in Methamphetamine-Dependent Subjects. Neuropsychopharmacology, 1, 53-63; Volkow, N.D., Fowler, J.S. (2000). Addiction a disease of compulsion and drive: involvement of the orbitofrontal cortex. Cerebral Cortex, 10, 318–325.

What these two groups have in common is poor impulse control. This faculty relies on the part of the brain called the prefrontal cortex, most particularly the orbitofrontal cortex. It is known that lesions to this part of the brain impair planning, prediction of consequences, and inhibition of socially unacceptable behaviour – the cognitive mechanisms of “free won’t”, rather than free will. These data thus suggest a specific disruption of the network connecting orbitofrontal cortex and amygdala in psychopaths, the degree of which correlated strongly with the subjects’ scores on the psychopathy checklist.

Example of DTI: Reconstructions of white matter tracts in a single healthy control: the left ILF in green, the left uncinate fasciculus in red, the left arcuate fasciculus in cyan, the left fronto-parietal SLF in blue, the genu of the corpus callosum in orange and the splenium of the corpus callosum in yellow. Tracts are superimposed onto the subject&amp;apos;s T1-weighted image normalized into the FA space. CC = corpus callosum. Dr. Linda Wang (&amp;/or Linda Wong) Unv. Of Hawaii with Dr. Nora Volkow.

NESARC = National Epidemiologic Survey on Alcohol and Related Conditions 10-12 yo first use is 5 times (500%) more likely to become addict than 17-18 yo first use and 17 times more likely than those who delay their first use until after their mid 20’s Source: Andres, G et al. Associations Between Early-Adolescent Substance Use and Subsequent Young-Adult Substance Use Disorders and Psychiatric Disorders Among a Multiethnic Male Sample in South Florida. Am J Public Health 94 (9): 1603 Source: Andres, G et al. Associations Between Early-Adolescent Substance Use and Subsequent Young-Adult Substance Use Disorders and Psychiatric Disorders Among a Multiethnic Male Sample in South Florida. Am J Public Health 94 (9): 1603 until mid 20s or later

Dr. John Hart Slide: From research described in the previous slide, it was discovered that drugs of abuse produce many of their abuse-related effects by activating the limbic system (shown in purple). This region is also responsive to natural rewards such as food, water, and sexual activity. In this simplified depiction, the brain is broadly divided into 2 areas – the outer cortex that is responsible for higher order thinking, executive functioning, and decision making AND the deeper regions of the limbic system that deal with primitive drives and All mammals and many lower order animals have a limbic system that is essential for survival and for experiencing the reinforcing effects of natural rewards such as food and water, but few mammals have a well-developed cortex psychosocial interventions have utility in altering pathological decision making in drug dependent individuals, but these interventions don’t address the underlying neurobiological changes in the limbic system that are responsible for craving and uncontrollable drug use. The combination of pharmacotherapies and psychosocial interventions afford a two-pronged approach to treating addiction. emotions. Addiction treatment field has been very effective treating just the conscious cortical component of addiction because of dedication and compassion of clinicians with prevailing attitude of unconditional positive regard for all suffering from addictive disorders.

This panel focuses on important regions of the limbic system that was shown in purple on the previous slide. The nucleus accumbens is the “center of the universe” for experiencing the reinforcing effects of drugs of abuse, and nearly all drugs of abuse activate the nucleus accumbens The neuronal projection from the VTA to the nucleus accumbens and prefrontal cortex comprises a major component of what is knows as the mesolimbic dopamine system. Dopamine-containing neurons in the VTA project to the NAcc and release dopamine there. This process is thought to produce sensations of pleasure and well-being. The VTA also sends projections to the prefrontal cortex, and dopamine release there also contributes to the reinforcing effects of drugs of abuse. The prefrontal cortex also receives input from other limbic brain regions thought to be involved in drug reinforcement, such as the amygdala, hippocampus, and anterior cingulate. The prefrontal cortex sends glutamatergic projections back to the nucleus accumbens. As such, the prefrontal cortex is a region that could integrate information from a variety of brain areas associated with drug reinforcement, and modulate responses of these brain areas to drug administration. It has been discovered that nearly all drugs of abuse increase nucleus accumbens dopamine, and for years, the prevailing hypothesis was that dopamine was the key neurotransmitter subserving the reinforcing effects of all drugs of abuse. In recent years, however, it has become apparent that dopamine is not the only “reward” neurotransmitter, and that other neurotransmitters play key roles. In support of this, destroying the dopaminergic projection from the VTA to the nucleus accumbens does not alter alcohol intake in animals. Clearly, other neurotransmitters are involved. Opioid peptides have also been shown to play an important role in alcohol intake. The arcuate nucleus of the hypothalamus contains opioid peptides which can be released and can bind to receptors in the nucleus accumbens and VTA. As such, opioid peptides are reward neurotransmitters in much the same way that dopamine is. Drs. Jennifer Mitchell &amp; Howard Field UCSF’s Gallo Institute Endorphin Study 1/12/12 fMRI show those prone to alcoholism release more endorphin in both the limbic system and the pre frontal cortex.

In fact, memories are the main driving force in every part of our daily lives.

“Footprints of Memory”, spikes, appendages, pimples?

Medieval (500-1500 ad) towns used 7-8 yo child selected to very carefully observe proceedings of an important event then thrown into a river to imprint the memories of the event in the child’s mind emotionally so that it would last a lifetime. (McGaugh, James L. [2003]. Memory &amp; Emotion: The Making of Lasting Memories. Columbia University Press, New Youk, NY)

They are retained as memory bumps or more precisely as dendritic spines. These protrusions grow when a dendrite is stimulated by a sensory input. If the input is intense, the dendritic spine, and therefore the memory becomes semi-permanent. The more we use it, the more permanent it becomes.

For example, this experiment bathed a nerve cell with estrogen, the main female hormone and then stressed the dendrite just as a big high might. As a result, the memory spines grew faster and bigger. Even adjacent spines grew and created the equivalent of a powerful memory network. When this process is mimicked by use of a psychoactive drug, the reward reinforcement circuit is hijacked.

This panel focuses on important regions of the limbic system that was shown in purple on the previous slide. The nucleus accumbens is the “center of the universe” for experiencing the reinforcing effects of drugs of abuse, and nearly all drugs of abuse activate the nucleus accumbens The neuronal projection from the VTA to the nucleus accumbens and prefrontal cortex comprises a major component of what is knows as the mesolimbic dopamine system. Dopamine-containing neurons in the VTA project to the NAcc and release dopamine there. This process is thought to produce sensations of pleasure and well-being. The VTA also sends projections to the prefrontal cortex, and dopamine release there also contributes to the reinforcing effects of drugs of abuse. The prefrontal cortex also receives input from other limbic brain regions thought to be involved in drug reinforcement, such as the amygdala, hippocampus, and anterior cingulate. The prefrontal cortex sends glutamatergic projections back to the nucleus accumbens. As such, the prefrontal cortex is a region that could integrate information from a variety of brain areas associated with drug reinforcement, and modulate responses of these brain areas to drug administration. It has been discovered that nearly all drugs of abuse increase nucleus accumbens dopamine, and for years, the prevailing hypothesis was that dopamine was the key neurotransmitter subserving the reinforcing effects of all drugs of abuse. In recent years, however, it has become apparent that dopamine is not the only “reward” neurotransmitter, and that other neurotransmitters play key roles. In support of this, destroying the dopaminergic projection from the VTA to the nucleus accumbens does not alter alcohol intake in animals. Clearly, other neurotransmitters are involved. Opioid peptides have also been shown to play an important role in alcohol intake. The arcuate nucleus of the hypothalamus contains opioid peptides which can be released and can bind to receptors in the nucleus accumbens and VTA. As such, opioid peptides are reward neurotransmitters in much the same way that dopamine is. Drs. Jennifer Mitchell &amp; Howard Field UCSF’s Gallo Institute Endorphin Study 1/12/12 fMRI show those prone to alcoholism release more endorphin in both the limbic system and the pre frontal cortex.

Metyrapone given to non-opiate users increase CRF and ACTH but has no effect in heroin addicts whose stress hypersensitivity had already turned off their cortisol. When given to abstinent opiate addicts who were not on methadone maintenance their ACTH levels increased as normies. Opiate addicts on methadone for 3 months or more also had normal increase ACTH response to metyrapone because they were no longer in a constant state of experience opiate withdrawal every 6-8 hours or so thus their stress cycle had normalized. Kreek and Koob (1998). Stress and dysregulation of brain reward pathway. Drug and Alcohol Dependence 51:23-47. Kreek et al. (1984). ACTH, cortisol, and b-endorphin response to metyrapone testing during chronic methadone maintenance treatment in humans. Neuropeptides, 5:277-278. CP-154,526 Pfizer labs blocks the actions of CRF. Heilig M and Koob GF (2007), A key role for corticotrophin-releasing factor in alcohol dependence. Trends Neurosci. 30(8):399-406, Lowery EG, Sparrow AM, Breese GR, Knapp DJ and Thiele TE (2008), The CRF-1 receptor antagonist, CP-154,526, attenuates stress-induced increases in ethanol consumption by BALB/cJ mice. Alchol Clin Cep Res, 32(2):240-248,

Discuss here or maybe better latter with the stop signal test slide. Titanic vs. Lusitania: How People behave in a disaster, Time Science 3/3/10 @ http://www.time.com/time/health/article/0,8599,1969142,00.html from Swiss and Austrian behavioral scientist published in Proceedings of the National Academy of Science Benno Torgler, economic professor of Queensland Univ. of Tech. Brisbane Australia is one of the authors. The Titanic with 2,207 passengers and a mortality rate of 68.7% sank about 3 years before Lusitania with 1,949 passengers and a mortality rate of 67.3%. Focus was on Third-Class passengers age 35 or older traveling without children as being most likely to die because: age, less fit, deep enough below deck to get to available lifeboats, and no children meant less motivated to survive and others to let them pass ahead. Death rate of this “reference group (rg)” compared to others. Results: Children under 16 were 31% likelier than reference group (rg) to survive on Titanic but on Lusitania they were 0.7% less likely to survive. Males 16-35 on Titanic had a 6.5% poorer survival rate than rg but a 7.9% better than rg on the Lusitania. Females 16-35 on Titanic 48.3% better survival than rg, Lusitania only10.4% better survival than rg. First Class Passengers were 43.9% more likely than rg to get into a life boat on Titanic and 11.5% less likely than rg on the Lusitania. NY Times 3/1/10 article states Children on Titanic were 14.8% more likely to survive than adults while on Lusitania they were 5.3% less likely to survive than adults. Women on Titanic were 53% more likely to survive than men, on Kusitania 1.1% less likely. Projected Explanation: Titanic sunk over 2 hours and 40 minutes or 160 minutes, Lusitania sank in 18 minutes. Time only for Selfish Rationality of flight response on Lusitania giving edge to strong younger males. On Titanic time was enough for good manners (women, children, elders, and even upper class first) had a chance to assert itself. Thus, before initiating any action to use during a trigger must give your brain time for more rational behavior.

Olds, James (1956) Pleasure centers in the brain. Scientific American. 105-116. James Olds and Peter Milner, &amp;quot;Positive Reinforcement Produced by Electrical Stimulation of the Septal Area and Other Regions of the Rat Brain,&amp;quot; Journal of Comparative and Physiological Psychology 47 (1954): 419-28. Newer rat research to prove addiction and not just conditioned behavior by Robinson, Terry E (2004), Addicted Rats, Science 305:951-955. He showed that lever pressing for cocaine by rats produced same addiction Cs as found in humans: no Control, Compulsion, Craving and Continued use despite Negative (Catastrophic) Consequences. Normie rats quit pressing lever if consequence was a painful shock . Progressive Ratio is different in normie rats, if they have to press too many times just to get a hit of cocaine they stop whereas addicted rats continue forever hoping to finally get a hit. His research showed that normie rats become addicted with progressive involuntary exposure to cocaine. Also, Incentive Sensitization Theory of Addiction. Robinson, Terry E and Berridge, Kent C. (2008), The incentive sensitization theory of addiction: some current issues. Philosophical Transactions of the Royal Society, 363:3131-3146, July 2008. Posits that addiction is caused by drug-induced sensitization in the brain mesocorticolimbic systems that attribute incentive salience to reward-associated stimuli. If rendered hypersensitive, these systems cause pathological incentive motivation (“wanting”) for drugs. AKA cravings that lead to recrudescence during attempted abstinence. Terry E. Robinson Phd from U of Western Ontario and now Professor of Psychology &amp; Neuroscience at U of Michigan.

Food Reward. Early experiments by James Olds located the heart of the reward/reinforcement pathway, the nucleus accumbens. He implanted an electrode in the mouse’s brain and saw it react to stimulation . The mouse kept pressing the lever again and again to continue the electrical stimulation. Dr. Olds and others such as Gerald McLaren wondered if psychoactive drugs could stimulate the reward/reinforcement center. They could.

Drug Reward. One experiment was to see how much a rat would go through for some cocaine. Every time the rat would push a lever, it would get a shot of cocaine. The animal would keep pushing the lever, even when it didn’t get a shot, in anticipation of the rush. It would push the lever thousands of times to get the shot or in anticipation of the shot.

Aversive electrical shock grid for reward of drug animals continue to respond and electrocute themselves. 2010 Update: Scripts Florida scientists used junk food instead of nutritious foods in similar operant conditioning rat experiments. Once addicted to junk foods (high fat bacon, sausage, cheesecake, pound cake, Ding Dong and cake frostings) rats were resistant to electro-shock aversive conditioning similar to that seen with cocaine, heroin, etc. Then when the unhealthy diet was replaced by the healthy diets they were raised on, the rats actually starved themselves to death rather than eat the healthy food. Dopamine D2 receptors were found to be down regulated by the high fat diet just like that seen in cocaine, heroin and other drug addictions. Johnson Paul M. &amp; Kenny Paul J. (7/9/2010), Dopamine D2 Receptors in addiction-like reward dysfunction and compulsive eating in obese rats. Nature Neuroscience 13:635-641. Some believe that such Faradic counter conditioning mechanisms do work in humans. Faradic Therapy or Aversion Therapy via TENS Units (Transcutaneous Electrical Nerve Stimulator)to deliver electric shock (named for Michael Faraday 1791 – mid 1800s). Schick-Shadel Smoking Centers Note these experiments are challenged by Dr. Bruce K Alexander’s (Simon Fraser Univ., Burnaby, BC, Canada) “Rat Park” research. Rats in lush cages with colored balls, best food, tunnels, lots of other rats consumed only 25% amount of drugs that isolated poor environment rats did. Those isolated rats given 57 days of use was put into his rat park and they stopped their heavy drug use. Alexander, B.K., Coambs, R.B., and Hadaway, P.F. (1978). &amp;quot;The effect of housing and gender on morphine self-administration in rats,&amp;quot; Psychopharmacology, Vol 58, 175–179

Heath, R. G. (1972). Pleasure and brain activity in man. Deep and surface electroencephalograms during orgasm, J Nerv Ment Dis 154 (1): pp. 3-18. In 1970, Heath also thought he could cure homosexuality by stimulating the NAc of a gay while a female prostitute got him excited (patient B-19).

we are not just treating drug usage Addiction is characterized by inability to consistently abstain, impairment in behavioral control, craving, diminished recognition of significant problems with one’s behaviors and interpersonal relationships, and a dysfunctional emotional response. Like other chronic diseases, addiction often involves cycles of relapse and remission. Without treatment or engagement in recovery activities, addiction is progressive and can result in disability or premature death.

Again, Bill Cohen: Addiction is Overactive Go Switch, Damaged Stop Switch, and Lack of Communication between the two switches.

Contacts between neurons Cadherin complexes are known to play diverse roles in a cell type-specific manner. In an ongoing study of cadherin-catenin function in interneuronal junctions, Takeichi&amp;apos;s lab has found that αN-catenin, a form of α-catenin specific to the nervous system, is essential to the stabilization of dendritic spines. These projections are important for establishing and maintaining contacts between axons and dendrites, the two principal types of extensions from the neuronal cell body. Previous work showed that cadherins help to regulate the adhesion of dendritic spines to axons, which is a crucial step in synapse formation, a finding which was complemented by this year&amp;apos;s elucidation of αN-catenin&amp;apos;s role. The functional loss of this molecule resulted in dramatic increases in spine motility and shape alterations, while αN-catenin overexpression caused spines, which normally extend and retract intermittently, to turn over at a much lower rate, resulting in abnormal accumulations of mature spines over time. Taken together, these results suggest that αN-catenin is a critical agent in maintaining the appropriate balance between stability and turnover in synaptic contacts. Multipolar, unipolar, bipolar Group Director Masatoshi Takeichi http://www.cdb.riken.go.jp/jp/04_news/annual_reports/2003/WebHelp/Takeichi_Lab.htm Tanabe K, Takeichi M, and Nakagawa S. Identification of a nonchordate-type classic cadherin in vertebrates: Chicken Hz cadherin is expressed in horizontal cells of the neural retina and contains a nonchordate-specific domain complex. Dev Dyn (2004). Abe K, Chisaka O, van Roy F, and Takeichi M. Stability of dendritic spines and synaptic contacts is controlled by αN-catenin. Nat Neurosci (2004). S Nakagawa, S Takada, R Takada and M Takeichi. Identification of the Laminar-Inducing Factor: Wnt-Signal from the Anterior Rim Induces Correct Laminar Formation of the Neural Retina in Vitro. Dev Biol 260:414-25 (2003). Kubo F, Takeichi M and Nakagawa S. Wnt2b controls retinal cell differentiation at the ciliary marginal zone. Development 130:587-98 (2003). Nakagawa S, Takada S, Takada R and Takeichi M. Identification of the laminar-inducing factor: Wnt-signal from the anterior rim induces correct laminar formation of the neural retina in vitro. Dev Biol 260:414-25 (2003). Togashi H, Abe K, Mizoguchi A, Takaoka K, Chisaka O and Takeichi M. Cadherin regulates dendritic spine morphogenesis. Neuron 35:77-89 (2002).

And since the number of dendrites, in a single nerve cell can vary from 10 or 20 in a pyramidal cell up to 10,000 in a purkinje cell . . .

These memories are retained on nerve cells, specifically on the dendrites of nerve cells. Astrocytes and glial cells

With 100 billion nerve cells and some quadrillion synapses, the brain’s complexity is unparalled. Messages travel in multiple directions with purpose, enabling the senses to transmit messages to the brain that, in turn, send commands back to the appropriate muscles, tissues, and organs. A single nerve cell can receive signals from hundreds, or thousands, of other nerve cells.

Message transmission occurs when the incoming electrical signal (1) forces the release of neurotransmitters (2) from the vesicles (3) and sends them across the synaptic gap (4) where they will slot into receptor sites (5). which cause an ion molecular gate (6) to open, allowing sodium (7), potassium, or chloride ionic electrical charges in or out. When the total voltage reaches 40–60 mv (millivolts), it fires the signal (8). Neurotransmitters are then released and reabsorbed by reuptake ports [9]) and returned to the vesicles, ready to fire again.

http://www.northland.cc.mn.us/biology/AP2Online/Nervous/nerve4.htm

More than 100 neurotransmitters have been discovered. The most well known are endorphins, dopamine, serotonin, and GABA. Psychoactive drugs can mimic these neurotransmitters. That is why these drugs affect us. Behaviors such as gambling and sexual activity can also activate these neurotransmitters. Types: amino acid (glutamate, GABA), peptides (endorphins, enkephalins), monoamine (dopamine, NorEpi, Epi, histamine, serotonin), Misc. (acetylcholine, anandamide, nitric oxide, adenosine)

Let’s look more closely on how the neurotransmitters, which help transmit messages, affect our drug craving and tendency to relapse. Synapses are 20 – 40 nm apart but a gap junction is only 3.5 nm, synapse occurs at ~230-280 mph.

Cocaine forces the release of extra neurotransmitters, especially dopamine, epinephrine, and norepinephrine. It then blocks the reuptake ports so the neurotransmitters cannot be reabsorbed by the sending neuron, thus causing excess stimulation of the user.

When heroin is taken, it slots into receptor sites on the edge of the pain-transmitting nerve cell, causing a reduction in the amount of substance P that crosses the gap. The heroin also slots into receptor sites on the receiving neuron, blocking the substance P that does get through. When heroin or opioid use is discontinued, pain returns unless the damaged tissue or organ has been repaired.

In terms of the reward/reinforcement center, dopamine is the most important neurotransmitter. It is sometimes called the reward neurotransmitter. It is dopamine which activates the nucleus accumbens, the go switch. It is also dopamine which also disrupts the stop switch.

Natural rewards increase dopamine neurotransmission. For example, eating something that you enjoy or engaging in sexual behavior can cause dopamine levels to increase. In these graphs, dopamine is being measured inside the brains of animals, its increase shown in response to food or sex cues. This basic mechanism has been carefully shaped and calibrated by evolution to reward normal activities critical for survival.

Drugs of abuse increase dopamine neurotransmission. All the drugs depicted in this slide have different mechanisms of action; however, all increase activity in the reward pathway by increasing dopamine neurotransmission. Because drugs activate these brain regionsusually more effectively than natural rewardsthey have an inherent risk of being abused.

Drs. Jennifer Mitchell &amp; Howard Field UCSF’s Gallo Institute Endorphin Study 1/12/12 fMRI show those prone to alcoholism release more endorphin in both the limbic system and the pre frontal cortex.

Also Takahashi, Hidehiko, Fujie, S, Camerer, C, Arakawa, R, Takano, H, Kodaka, F, Fatsui, H, et al. of Kyoto University (2/21/2012), Norepinephrine in the brain is associated with aversion to financial loss, Molecular Psychiatry, 18, 3-4 links pathologic gambling with lower level of norepinephrine transporters in reward/reinforcement circuit of limbic system. This results in greater amount of norepinephrine there that leads them to be less aroused by losses and less sensitive to the pain of losing money. Research done by PET scans.

The discovery in rodents — published today in Nature Communications — shows that stimulation of glutamate neurons in a specific brain region (the dorsal raphe nucleus) leads to activation of dopamine-containing neurons in the brain’s reward circuit (dopamine reward system). Dopamine is a neurotransmitter present in regions of the brain that regulate movement, emotion, motivation, and feelings of pleasure. Glutamate is a neurotransmitter whose receptors are important for neural communication, memory formation, and learning. The research was conducted at the Intramural Research Program (IRP) of the National Institute on Drug Abuse (NIDA), which is part of the National Institutes of Health. The research focused on the dorsal raphe nucleus, which has long been a brain region of interest to drug abuse researchers, since nerve cells in this area connect to part of the dopamine reward system. Many of the pathways are rich in serotonin, a neurotransmitter linked to mood regulation. Even though electrical stimulation of the dorsal raphe nucleus promotes reward-related behaviors, drugs that increase serotonin have low abuse potential. As a result, this region of the brain has always presented a seeming contradiction, since it is involved in drug reward but is also abundant in serotonin - a chemical not known for a role in drug reinforcement. This has led researchers to theorize that another neurotransmitter may be responsible for the role that the dorsal raphe nucleus plays in reward. In these rodent models, researchers used special tracers and labelling compounds to confirm that this circuit in the reward pathway begins with glutamate cells in the dorsal raphe nucleus that connect to dopamine cells in the ventral tegmental area, which in turn travel to the nucleus accumbens, a brain structure linked to motivation, pleasure, and reward. After verifying the pathway, investigators used optogenetic techniques (using light to control activity of modified cells) and chemical blockers to confirm that glutamate, not serotonin, is responsible for activating this reward circuitry. The paper by Qi et al. can be found at http://www.nature.com/ncomms/index.html . For similar research currently being conducted by NIDA IRP in this area, go to: http://irp.drugabuse.gov/cnrb.php#Anchor-Anatomy-48213.

Now see impact on addiction pathway, cognition, allostasis, craving, relapse potential and even severity and reality of pain

First fMRI using oxygen as a contrast media to create BOLD fMRI was in 1990 by Seiji Ogawa at AT&amp;T Bell labs

Scans of the brain can reveal how the brain tries to repair itself. Functional MRi scans and SPECT scans can show increased activity in the brain or the presence of dopamine, or the absence of dopamine receptor sites. CAT, PET, MRI, fMRI, DTI, SPECT

Anatomical (Structure Computed tomography (CT) or Computed Axial Tomography (CAT) scanning uses a series of x-rays of the head taken from many different directions Diffusion MRI (dMRI) is a magnetic resonance imaging (MRI) method which came into existence in the mid-1980s. It allows the mapping of the diffusion process of molecules, mainly water, in biological tissues, in vivo and non-invasively. Molecular diffusion in tissues is not free, but reflects interactions with many obstacles, such as macromolecules, fibers, and membranes. Water molecule diffusion patterns can therefore reveal microscopic details about tissue architecture, either normal or in a diseased state Diffusion tensor imaging (DTI) is a type of diffusion MRI used so that functions in the brain may be observed as they occur, (in vivo). The restricted diffusion of water through the brain tissue under examination is measured; it is often used to image white matter Magnetic Resonance Imaging (MRI) uses magnetic fields and radio waves to produce high quality two- or three-dimensional images of brain structures without use of ionizing radiation (X-rays) or radioactive tracers MRI –GUI (Graphical User Interface) preoperative imaging information is subject to errors resulting from brain shift and deformation in the Operating Room. GUI facilitates the flow of data from OR to image volume in order to provide the neurosurgeon with updated views concurrent with surgery. X-Ray Functioning Arterial spin labeling (ASL) in neuroimaging, is a magnetic resonance imaging technique for measuring tissue perfusion (brain metabolism) using a freely diffusible intrinsic tracer. Diffuse Optical Imaging (DOI) or Diffuse Optical Tomography (DOT) is a medical imaging modality which uses near infrared light to generate images of the body. The technique measures the optical absorption of haemoglobin, and relies on the absorption spectrum of haemoglobin varying with its oxygenation status Electroencephalography (EEG) is the recording of electrical activity along the scalp. EEG measures voltage fluctuations resulting from ionic current flows within the neurons of the brain. (measures brain electrical activity) Event-Related Optical Signal (EROS) is a brain-scanning technique which uses infrared light through optical fibers to measure changes in optical properties of active areas of the cerebral cortex Functional Magnetic Resonance Imaging (fMRI) and arterial spin labeling (ASL) relies on the paramagnetic properties of oxygenated and deoxygenated hemoglobin to see images of changing blood flow in the brain associated with neural activity. (measures brain metabolism) Bold fMRI very high resolution brain images (65 × 65 × 700 μm3) acquired with a gradient-echo pulse sequence complements other techniques that are attempting to provide positron emission tomography-like measurements related to regional neural activity Magnetoencephalography (MEG) is an imaging technique used to measure the magnetic fields produced by electrical activity in the brain via extremely sensitive devices such as superconducting quantum interference devices (SQUIDs). (measures brain electrical activity) Positron Emission Tomography (PET) measures emissions from radioactively labeled metabolically active chemicals that have been injected into the bloodstream. (measures neurotransmitters and receptors) Single-Photon Emission Computed Tomography (SPECT) is similar to PET and uses gamma ray-emitting radioisotopes and a gamma camera to record data that a computer uses to construct two- or three-dimensional images of active brain regions (neurotransmitters and receptors) Statistical parametric mapping (SPM) is a statistical technique for examining differences in brain activity recorded during functional neuroimaging experiments using neuroimaging technologies such as fMRI or PET. It may also refer to a specific piece of software to carry out such analyses.

One thing the scans show is that the more drug used, the more alcohol drunk, the more bets made, especially over a period of time, the greater the shutdown of the brain. The brain of a young heavy drinkers shows almost a complete shutdown of most activity. Alcohol is a depressant. Even with other addictions, the disruption of the brain is obvious. Susan Tapert f MRI scan Feb. 2004

These are actual scans of the density of dopamine receptors in the brains of normal people versus those who are dependent on some psychoactive drug or compulsive behavior. Notice that all addictions show a reduction in the number of receptor sites and therefore an increased need for excess dopamine and therefore an increased craving for extra amounts of the drug to release sufficient dopamine to create the desired feeling. Wang, G-J, Volkow, ND, Panayotis, TK and Fowler, JS (2004). Similarity between obesity and drug addiction as assessed by neurofunctional imaging: A concept review. J. of Addictive Disease, 23(3)39-53.

Earlier slide of PET scan showing subcortical brain activation by cocaine. These are PET scans of a person’s brain on cocaine. The yellow areas are where cocaine is exciting the brain, giving a rush. At 6 to 8 minutes there is maximum involvement in all areas and then it starts to diminish. At 20 to 30 minutes, it has spent its major effects. This progression is similar to the effect the anticipation to gamble has on the brain of a gambler. In that case, two forms of adrenaline and dopamine are released, and it takes 20 to 30 minutes for that adrenaline to be reabsorbed. This means that when a craving pops into our head, we need to do something to let 20 to 30 minutes pass to let the adrenaline be reabsorbed. There dozens of activities that we can use . . . .

SPECT, or “single photon emission computerized tomography,” is an imaging technique showing areas of activity and inactivity in the brain. The “holes” are actually areas that are inactivated by the use of a drug or the practice of some behavior. Abstinence restores much, but not all, of the brain function. The more chronic the use, the less the restoration of activity. Methamphetamine is more toxic than heroin or cocaine. Image courtesy of Daniel Amen, M.D.

Because alcohol is a protoplasmic poison, much of the inactivation in the brain of a chronic alcoholic can be long lasting, or permanent. Heroin is less toxic to brain cells, so abstinence restores more brain function. Image courtesy of Daniel Amen, M.D.

SPECT, or “single photon emission computerized tomography,” is an imaging technique showing areas of activity and inactivity in the brain. The “holes” are actually areas that are inactivated by the use of a drug or the practice of some behavior. Abstinence restores much, but not all, of the brain function. The more chronic the use, the less the restoration of activity. Methamphetamine is more toxic than heroin or cocaine. Image courtesy of Daniel Amen, M.D.

In the winning phase, gamblers are confident they can make a living gambling. In the losing phase, they start to chase their losses and gamble poorly. In the desperation phase, their debts mount, they gamble foolishly, and they will do anything to keep gambling. In the giving-up phase,they stop believing they will win it all back but want to stay in action so they don’t have to think.

The basic characteristics of a drug abuser are similar to those of a compulsive gambler. There is a gene (DRD2A1 allele) that show’s a predisposition to alcoholism, drug addiction, and gambling. Discuss ego and entitlement difference in Gambling Use Disorder vs. Substance Use Disorder and the Gambler’s illusion of being able to control the outcome of random events

The easy access to the Internet, the ability to use it in isolation, the anonymity while using, and the low cost make the Internet as potentially powerful as any drug addiction. Online pornography, relationship chat rooms, hundreds of gambling sites, and thousands of computer games feed into a compulsive user’s addiction. (pp. 352–354)

Researcher Lucy Brown, Albert Einstein College of Medicine puts people who are madly in love into an MRI and asks them to think about their beloved. Subjects tend to show activity in the ventral tegmental area (left arrow), associated with euphoria and addiction. This subject also has activity in the prefrontal cortex (right arrow), associated with thinking and reward. Dr. Helen Fisher, Biological Anthropologist, Rutgers Univ. : dopamine (also with nor epi and serotonin) is neurotransmitter of attraction and romantic love junkies, serotonin is attachment junkies, testosterone is rage, violence, sex drive, domestic abuse and stalking, estrogen is chemical depression. Rejection pain involves NAcS, Anterior Insula, and Mid Orbital Frontal Cortex &amp; Gyrus (craving). Stages of Rejection = I. protest, stress response, abandonment, rage, stalking, rage suicide II. Resignation, depression, despair suicide As dopamine increases so does testosterone and nor epinephrine. Any manipulation of genitals increase dopamine. As serotonin increases dopamine decreases Romantic Love has develops intensification, tolerance, and withdrawal. After romantic break up men commit suicide 2.5 times more than women.

2011 new ASAM definition of Addiction = Reward Deficiency Disorder.

National Geographic November 2014 Zombie Parasites Nature’s Nightmare Mind Suckers: My analogy: Zombie Parasitic infection is like Addiction – the brain gets hijacked into doing things its doesn’t want to do, threatens survival and eventually result in catastrophic consequences even death. Recovery is about brain ownership, regaining ones hijacked brain so that it can again promote better life experiences and survivability Paragordius vanus, horsehair worm: larvae of the parasite grow into adult worms inside House Crickets (or grasshoppers). They can only feed on the cricket but live and mate in an aquatic environment. So when they reach adulthood in the cricket it alters their brains to jump into fresh water to commit suicide then the foot long up to a yard long thin worms quickly emerge from the dead cricket to mate, female lay eggs that develop into larvae within 2-4 weeks and are they are ingested by an aquatic animal. Inside the transport host (fish, snail, aquatic insect larvae, etc.) it forms a sturdy cyst that is viable for at least a year. How the cyst gets into crickets is not fully known but it is projected that aquatic insect larvae (e.g. mosquitoes or flys) morph into flying insects, that carry the cyst outside of the water and when they die are eaten by crickets and complete the life cycle of the worm. Pseudocorynosoma constrictum, thorny-headed worm: can only grow to maturity inside the guts of waterfowl. Larvae of this worm invades Hyalella azteca, a tiny amphipod that that only lives in the murky bottom of lakes and ponds. When the larva matures, it causes the amphipod to swim towards the light of the surface of the pond which make it easy prey for waterfowl. In the duck , egret, etc. the larva matures into an adult in their intestine and lays eggs that are then dropped into lakes in ponds via their feces. The eggs or embryos are then ingested by amphipod to complete the cycle. Ophlocordyceps spp. Fungus: spores of this fungus infest ants like the Dinoponera longipes or Amazonian ant. The fungus then grow in the ant infecting its brain and compelling it to leave its normal habitat the forest floor and climb into trees to fasten itself to a leaf or bark. As the fungus then eats up the ant, its spores rain down on the forest floor giving it a better chance to infect more ants. Ribeiroia ondatrae flatworm: invades snail reproductive organs where it produces its larvae. The larva leave the snail and dig into the developing limbs of tadpoles (i.e. Lithobates catesbelanus, American bullfrog). The infected legs of the tadpole cause gross deformities in its legs making the frog incapable of avoiding danger. They are eaten by frog eating birds where the parasite reproduces sexually producing eggs that are spread into lakes in ponds via feces to hatch into larvae to infect snails. Toxoplasma gondii protozoa: only reproduces in a cat’s intestinal tract to form oocysts that is excreted with its feces. Rats, mice and other mammals (including humans and pigs) and even some birds can get infected with the oocyts by eating food contaminated with cat feces. There the oocyst hatch to form tissue cysts which can be passed to humans when under cooked pork is eaten.The main intermediate host is the rat/moose – when infected the cysts hatch into the protozoa that affect their brains to make them become attracted to the smell of cat urine which they usually avoid making the rodent easy prey for the cat to capture and eat where the parasite will reproduce in their intestines. Humans can also get infected by exposure to the feces of an infected cat’s feces (e.g. cat box where the cysts might scatter on to food, drink or other place where it can be unknowingly ingested. T. gondii also infect the brain of humans to cause unusual behaviors: Those with latent non-symptomatic infections are more likely to have traffic accidents; infected women are more likely to attempt suicide, infected men find the smell of cat urine more attractive, infected humans are more likely to have schizophrenia. As with addictive drugs, infected mice have elevated levels of dopamine.

NIDA Components of Comprehensive Drug Abuse Treatment: from top and clockwise – Child Care Services, Vocational Services, see next slide.

But, unfunded ideal as usual and we will see how this paradigm currently stacks up to treatment delivery.

Current issues in treatment concern medications, new ways to visualize the brain and diagnose the addicted person, a search for better and more culturally relevant treatment, and the continuing debate over harm-reduction strategies.

Treatment saves money, especially when compared to the cost of incarceration. Drug courts cost under $3,000 per individual compared to $20,000 to $30,000 per year for incarceration. In the past, state and federal governments skimped on allocating funds for treatment but recently, the use of drug courts and other treatment strategies has increased the funds available. (p. 441)

The direct costs of drug abuse (health problems, relationship problems, violence) extend to the costs of crime on our society. From 50% to 70% of all those incarcerated had drugs in their systems when arrested. Similar rates are seen in domestic abuse and rape.

Surgeon George, Mission Manuel Story?

Andrea Barthwell Medical Director for ONDCP under George W. presented at Genesis’ third annual New Connections Conference April 17-18, 2008 UFDS = Uniform Facility Data Set, TEDS = Treatment Episode Data Set Also a huge Treatment Gap- only about 1/26 of those in the U.S. who meet diagnostic criteria for addiction treatment get treatment every year.

Detox – Medical and/or Social Model care to manage acute withdrawal and cravings, getting drugs out of system Initial Abstinence – Medical and/or clinical interventions to rebalance body and neurotransmitters to promote continued abstinence and prevent slips/relapses from endogenous &amp; environmental triggers Long-Term Abstin. – Continued Medical and/or clinical interventions to address medical, social, psychological and even spiritual issues from the addiction, prevent slips and relapses on long-term basis Recovery – Life-long process of abstinence via new and much appreciated sober life and living habits, discovery of fun, exciting and fulfilling sober activities

This is a typical treatment protocol for client intake at an outpatient facility. It emphasizes the complexity of drug treatment, often involving medical and psychiatric intervention, counseling, pharmaceutical interventions, and group therapy.

Detoxification can unpleasant, painful, and in some instances - life threatening. Medical intervention is often necessary in cases of potentially fatal detoxification. Narcan (naloxone) is used for heroin overdoses, phenobarbital for alcohol and sedative-hypnotic withdrawal seizures, and antipsychotics for stimulant-induced psychoses.

The sight, smell, or memory of drug-using activities are the biggest triggers for relapse. These can send a recovering user back to the streets and a drug-using dysfunctional lifestyle. In recovery, one of the main goals is learning how to avoid triggers and what to do if a craving is activated by a sight, sound, smell, or memory. The use of groups (facilitated or self-help) is necessary during initial counseling. Anti craving drugs are also powerful adjuncts to the process.

Long-term abstinence is difficult, because cravings can occur at any time. Someone who has been addicted needs to be reminded daily that he or she is always susceptible to relapse - their allergy can be retriggered with just one drink, one hit, one puff. It might take several weeks of intermittent use, but 95% of addicts who slip, relapse..

Recovery is a lifetime process, so changing one’s lifestyle is essential to avoiding relapse. An addiction consists of an allergy to the substance along with a mental obsession to trigger that allergy. Recovery concentrates on the mental obsession. Medication therapy focuses on the allergy.

Only single celled animals and plants for 3.5 billion years then Cambrian Explosion of multi-cellular plants and animals 500 million years ago. These needed specialized cells to coordinate their multiple cell - neurons evolved Important because addiction starts in in unconscious, instinctive, reactive, unthinking, survival oriented diencephalon and mammalian mesocortex. Discuss here or maybe better latter with the stop signal test slide. Titanic vs. Lusitania: How People behave in a disaster, Time Science 3/3/10 @ http://www.time.com/time/health/article/0,8599,1969142,00.html from Swiss and Austrian behavioral scientist published in Proceedings of the National Academy of Science Benno Torgler, economic professor of Queensland Univ. of Tech. Brisbane Australia is one of the authors. The Titanic with 2,207 passengers and a mortality rate of 68.7% sank about 3 years before Lusitania with 1,949 passengers and a mortality rate of 67.3%. Focus was on Third-Class passengers age 35 or older traveling without children as being most likely to die because: age, less fit, deep enough below deck to get to available lifeboats, and no children meant less motivated to survive and others to let them pass ahead. Death rate of this “reference group (rg)” compared to others. Results: Children under 16 were 31% likelier than reference group (rg) to survive on Titanic but on Lusitania they were 0.7% less likely to survive. Males 16-35 on Titanic had a 6.5% poorer survival rate than rg but a 7.9% better than rg on the Lusitania. Females 16-35 on Titanic 48.3% better survival than rg, Lusitania only10.4% better survival than rg. First Class Passengers were 43.9% more likely than rg to get into a life boat on Titanic and 11.5% less likely than rg on the Lusitania. NY Times 3/1/10 article states Children on Titanic were 14.8% more likely to survive than adults while on Lusitania they were 5.3% less likely to survive than adults. Women on Titanic were 53% more likely to survive than men, on Kusitania 1.1% less likely. Projected Explanation: Titanic sunk over 2 hours and 40 minutes or 160 minutes, Lusitania sank in 18 minutes. Time only for Selfish Rationality of flight response on Lusitania giving edge to strong younger males. On Titanic time was enough for good manners (women, children, elders, and even upper class first) had a chance to assert itself. Thus, before initiating any action to use during a trigger must give your brain time for more rational behavior.

This panel focuses on important regions of the limbic system that was shown in purple on the previous slide. The nucleus accumbens is the “center of the universe” for experiencing the reinforcing effects of drugs of abuse, and nearly all drugs of abuse activate the nucleus accumbens The neuronal projection from the VTA to the nucleus accumbens and prefrontal cortex comprises a major component of what is knows as the mesolimbic dopamine system. Dopamine-containing neurons in the VTA project to the NAcc and release dopamine there. This process is thought to produce sensations of pleasure and well-being. The VTA also sends projections to the prefrontal cortex, and dopamine release there also contributes to the reinforcing effects of drugs of abuse. The prefrontal cortex also receives input from other limbic brain regions thought to be involved in drug reinforcement, such as the amygdala, hippocampus, and anterior cingulate. The prefrontal cortex sends glutamatergic projections back to the nucleus accumbens. As such, the prefrontal cortex is a region that could integrate information from a variety of brain areas associated with drug reinforcement, and modulate responses of these brain areas to drug administration. It has been discovered that nearly all drugs of abuse increase nucleus accumbens dopamine, and for years, the prevailing hypothesis was that dopamine was the key neurotransmitter subserving the reinforcing effects of all drugs of abuse. In recent years, however, it has become apparent that dopamine is not the only “reward” neurotransmitter, and that other neurotransmitters play key roles. In support of this, destroying the dopaminergic projection from the VTA to the nucleus accumbens does not alter alcohol intake in animals. Clearly, other neurotransmitters are involved. Opioid peptides have also been shown to play an important role in alcohol intake. The arcuate nucleus of the hypothalamus contains opioid peptides which can be released and can bind to receptors in the nucleus accumbens and VTA. As such, opioid peptides are reward neurotransmitters in much the same way that dopamine is. Drs. Jennifer Mitchell &amp; Howard Field UCSF’s Gallo Institute Endorphin Study 1/12/12 fMRI show those prone to alcoholism release more endorphin in both the limbic system and the pre frontal cortex.

Dr. John Hart Slide: From research described in the previous slide, it was discovered that drugs of abuse produce many of their abuse-related effects by activating the limbic system (shown in purple). This region is also responsive to natural rewards such as food, water, and sexual activity. In this simplified depiction, the brain is broadly divided into 2 areas – the outer cortex that is responsible for higher order thinking, executive functioning, and decision making AND the deeper regions of the limbic system that deal with primitive drives and emotions. All mammals and many lower order animals have a limbic system that is essential for survival and for experiencing the reinforcing effects of natural rewards such as food and water, but few mammals have a well-developed cortex psychosocial interventions have utility in altering pathological decision making in drug dependent individuals, but these interventions don’t address the underlying neurobiological changes in the limbic system that are responsible for craving and uncontrollable drug use. The combination of pharmacotherapies and psychosocial interventions afford a two-pronged approach to treating addiction.

Some use classic therapies of Adler, Glasser, Erickson, et. Al.

CBT addresses dysfunctional emotions, behaviors and cognitions through a goal-oriented, systemic process. Premise is that changing maladaptive thinking or one’s relationship to maladaptive thinking leads to changes in affect and behavior. William Miller (UoNM) &amp; Stephen Rollick (Cardiff U Britain) refined Motivational Interviewing/Enhancement Therapy in 1991. James Prochaska &amp; Carlo DiClemente, U of Rhode Island developed Levels of Change in late 70s-early 80s. Dialectical Behavior Therapy (DBT) developed by Marsha M. Linehan at UW combines CBT with mindfulness meditation. Creation of therapeutic alliance to validate client feelings every time while informing them that some of their feelings may be maladaptive and suggesting better alternatives. This is combined with mindfulness, capacity to pay attention, non-judgmentally, to the present moment. Living in the moment, experiencing one’s emotions and senses fully, yet with perspective.

Quickly evolving profession of Recovery Coach aka mentor, sober companion, sober escort etc. Akin to Life or Business Coach professions Credentialing required in many states and also state specified as to what these can and can not do. Average annual salary as of May 30, 2014 is stated to be $60,000 http://www.simplyhired.com/salaries-k-recovery-coach-jobs.html accessed 5/30/14

Withdrawal Assessment Tool-1 (WAT-1) assesses and monitors opioid and benzo withdrawal symptoms in pediatric patients Modified Selective Severity Assessment Detoxification Scoring (MSSA) assesses opioid, benzo and alcohol withdrawal symptoms, about 30-31 total points but arc will start medical assisted treatment at score of only 3 because Dr. Shames doesn’t want clients to be uncomfortable in residential so that we can better engage them in treatment

Cue-induced reinstatement of ethanol-seeking. During a phase of conditioning rats acquire stable lever pressing for ethanol in the presence of a distinct set of cues. After extinction, the animals are again exposed to the respective cues, formerly associated with ethanol, leading to renewed responding on the ethanol lever in the absence of the primary reinforcer (CTRL). Treatment with naltrexone (NAL; 0.25 mg/kg) or acamprosate (AC; 200 mg/kg) leads to a significant reduction of ethanol-seeking behavior. (Katner et al. (1999) Neuropsychopharmacology 20: 471-479; Bachteler et al. (2005) Neuropsychopharmacology; in press). (B) Reinstatement paradigm. Each lever press is followed by a 25-30% drop of ethanol as primary reinforcer.

Ondansetron (Zofran®) research: The American Journal of Psychiatry. 1/19/11 Bankole A. Johnson, M.D., D.Sc., from the University of Virginia in Charlottesville, and colleagues randomized 283 alcoholics in a double-blind controlled trial. Participants underwent genotyping in the serotonin-transporter-linked promoter region (5&amp;apos;-HTTLPR) of the 5-HTT gene (LL/LS/SS), and for a functional single nucleotide polymorphism (T/G) rs1042173 in the 3&amp;apos; untranslated region. Participants received 4 µg/kg ondansetron twice daily or placebo for 11 weeks, and standard cognitive-behavioral therapy. Among ondansetron recipients with the LL genotype, the number of drinks per drinking day was lower and the percentage of days of abstinence was higher compared with individuals with the LL genotype who received the placebo, or with individuals with LS or SS genotype who were treated with ondansetron. The 5-HTT genotype and rs1042173 polymorphism interacted significantly. LL/TT individuals treated with ondansetron had the lowest number of drinks and highest number of days of abstinence compared with all other genotype and treatment groups. Also report from France Dr. Philippe January 4/15/12 on the use of baclofen (Lioresal) to curb alcohol craving confirming earlier studies by Dr. Giovanni Addolorato, MD, from the Institute of Internal Medicine, Catholic University of Rome, Italy Lancet. (12/8/2007); 370:1915-1922,1884-1885. Also Explain “Off-Label” use of medications. Namefene (Selincro®) released in Europe for craving May 2013; Blocks opioid kappa receptors in VTA to block dopamine release Flumazenil (Romazicon®)

Varenicline: partial α4β2 agonist of nicotinic acetylcholine receptor and full agonist of α7 receptor thus blocking the ability of nicotine to stimulate the CNS mesolimbic dopamine system. Bupropion: α3β4 nicotine receptor antagonist, decreases morphine and methamphetamine as well in rats. It is a dopamine and norepinephrine reuptake inhibitor but dopamine is inactivated by Norepinephrine reuptake in the frontal cortex. Nortriptyline (Aventyl®, Pamelor) clondine (Catapres®)

Unsure if overall beneficial and no good impact studies. Conflicting studies on whether it makes it easier to detox and remain in recovery when tobacco as well as DOC is addressed. Best for client if they remain in treatment if too many drop out as Ohio women’s program report: 1. completion rate went from 70% 18 months before the ban to 42% during the first 3 months of the ban a swing of 28% and an actual 40% drop impact on treatment completions. 2. Importantly, non-smoker as well as smokers had greater non-completion rates. Only 20% of smokers and 7% of non-smokers dropped out prior to the ban followed by 42% (more than doubling drop outs) of smokers and 22% (more than tripling the drop outs) of non-smokers after the ban was instituted. ARC experience is chaos caused by policing and enforcing the ban was too much for non-smokers to deal with. Join Together (2012), Tobacco-free policies may reduce completion rates at substance abuse treatment centers. The Partnership At Drugfree.org, 5/6/11 http://www.drugfree.org/join-together/addiction/tobacco-free-policies-may-reduce-completion-rates-at-substance-abuse-treatment-centers Clark-Hammond, G., &amp; Gregoire, T. (2011) Breaking Ground in Tobacco Dependence at a Women’s Treatment Center. Journal of Social Work Practice in the Addictions, 11, (1), 1-16. May 2011 (study at Ohio’s Women’s Program) The study found that after the center’s implementation of a tobacco-free policy, the number of women who completed a program at the center dropped 28 percent, from 70 percent in the 18 months before the ban, to 42 percent within the first three months after the ban took effect. While 20 percent of smokers and 7 percent of nonsmokers checked out of the center early when smoking was allowed, early checkouts increased to 42 percent of smokers and 22 percent of nonsmokers after the ban was implemented.

Buprenorphine is addictive, #1 opioid abused drug in Nepal and India. Sontac, Deborah (11/16/13). Addiction Treatment with a dark side, NY times documents addiction, street demand/diversion, and potential involvement in 420 OD deaths in US since 2003 – 2013. [actually documents safety compared with the # of methadone, heroin, Vicodan, Oxycontin deaths over the same period of time]

Wall Street Journal 7/5/12 page B3 North Carolina and some internet postings claim one can inject Suboxone via triple washing of the SL Film dosage form.

Note that the huge majority of methadone deaths were in patients treated for pain with it, not in addiction replacement therapy. Also, over half of the deaths involved benzodiazepines combined with methadone.

2011 NSDUH and other surveys showing decline in Rx drug abuse most likely due to increased monitoring of who is prescribed, who prescribes and high risk medication protocols.

Reports indicate methadone deaths may have peaked out in 2007 but remains stagnant through 2010.

SOURCE: Automation of Reports and Consolidated Orders System (ARCOS) of the Drug Enforcement Administration (DEA), 2010

SOURCE: National Vital Statistics System, 2008

Drug Use Epidemic in US Shifting 6/15/12 http://hondurasweekly.com/drug-use-epidemic-in-us-shifting-201206155315/ Second to marijuana when not counting alcohol or nicotine or caffeine as drug abuse problems.

Reports indicate methadone deaths may have peaked out in 2007 but remains stagnant through 2010.

This was done by undercover Glendora, CA, Sheriff deputy on Dr. Rolando Losdevico Atiga on July 13, 2012.

1995 Oregon Intractable Pain Treatment Act. 2001 Michigan was first state to remove Intractable reference in its act making the regulation apply to all general pain issues. Many States revised their refulations in 2011 in accordance with the U of Wisconsin School of Medicine’s recommendations. https://www.atrainceu.com/course-module/1473265-63_oregon-pain-management-module-02 accessed 11/9/13di

I like 5 point Likert Scales because it has a true middle or ~normal level

0 no pain, difficulty or excellant to 10 extreme pain, difficult or poor All their materials are patient centered, icon coded, easy to process and programmed on a disk that will do analysis, track and graph record of responses. Follow – ups for next visit includes tests, treatment, date, behavior restrictions, diet restrictions, and recommendations (bed rest, walk, etc.) Pharmacist CARE Program (Compassionate Accurate Responsive Education) includes time and dose of meds to take (with or without food), things to avoid, potential side effects, storing &amp; Disposal of meds Daily Activity Checklist Fibro Log – log of items that affect pain Health care visit preparation check list 10 Steps to move from being a patient to being a person again Opioid constipation conversation assessment and guide Arthritis Ability Assessment Chart Managing Breakthrough Pain (BTP) Guide Managing Low Back Pain Guidelines Managing Fibromyalgia Pain Checklist and Guide, also Handbook, Tips, and 101 informational Booklet Understanding Nerve Pain Brosure and many other helpful materials for those suffering from chronic pain. Management of Pain not Elimination of Pain is emphasized, need for focus on reclaiming life that has been interrupted by chronic pain, understanding and acceptance that normal quality of life is work/volunteer daily, normal daily activities, social life outside of work, active participation in family life. Functionality is the target of chronic pain management not the pain and bed rest may be useful for acute pain but not inactivity is bad for chronic pain. Opiates ineffective in chronic pain and chronic pain is not opioid deficiency. Dr. John Loeser, MD - Univ. of Washington. Am. Chron. Pain Ascn. 10 Steps to Management of Chronic Pain: 1. Accept Pain 2. Get Involved in its management 3. Set Priorities to get back to an active life 4. Set Realistic Goals that are Specific, Measurable, Attainable, Relevant, Time Bound (SMART) 5. Know your basic rights (to be treated with dignity and respect, to say no without guilt, etc.) 6. Recognize your emotions, your pain impacts entire family 7. Learn to Relax 8. Exercise 9. See the Total Picture – focus on what you can still do 10. Reach Out. Penny Cowan Founder ACPA Rocklin, CA. A life of value in a life uninterrupted by pain. 25% of US have persistant chronic pain Those with chronic pain often direct their lives towards pain management and away from areas that bring meaning to their lives. Valued living does not require being pain free. People who have something to do don’t suffer as much. Dr. Kevin Vowles Clinical/Health Psychologist - Univ. New Mexico Albuquerque

~9% of all marijuana users develop addiction to marijuana. NIH NIDA http://www.drugabuse.gov/news-events/news-releases/2013/10/medication-to-treat-marijuana-addiction-may-be-horizon accessed 11/12/13di Treatment Episode Data Set (TEDS) table 1.1a page 43 2012 (but most resent data analyzed was through 2010) National Survey of Substance Abuse Treatment Services (N-SSATS) 335,833 of 1,820737 treated for substance use problems in 2010 (18.4%) this is most recent data available in 3/2014 Tom McClellan in CNBC Prime Interview 3/16/14 firmly states 10% of marijuana users will become addicted.

Controversy as to whether THC causes a significant release of dopamine in the striatum to result in addiction and vulnerability to schizophrenia. IV THC shown to release dopamine and several studies demonstrate an association with development of thought disorders. (Stokes PR, Mehta, MA, Curran, HV, Breen, G, &amp; Grasby, PM [2009]. Can recreational doses of THC produce significant dopamine release in the human striatum? Neuroimage, 48[1], 186-90, October 15, 2009) Remind THC&amp;lt; 7mg. = low dose; 7 – 18mg. = medium and &amp;gt;18mg. = high dose, one joint not steadily smoked and often shared with others but still, all can receive a high dose exposure these days.

The brain is remarkably resilient, flexible, plastic, and moldable = neuroplasticity Longer participation in continuous treatment continue to increase positive results but not at rate seen with 8-10 months so best bang for $ is that treatment period

In these scans of recovering cocaine addicts one can see how long it takes for the brain to recover normal activity. You can see that even at 100 days, the brain is functioning only at a fraction of its full potential. This means that even after stopping, it takes months for brain chemistry to return to a semblence of normalcy. Some say that it takes 8 months to a year for a cocaine users brain to return to even close to normal functioning. This recovery is similar to the recovery of a compulsive gamblers brain.

Some addictions have a greater affect on brain chemistry. Methamphetamine is quite toxic to nerve cells and so it can take 2 years or more for the brain to return to a semblence of normal. This doesn’t mean that the person is only as susceptible as when he or she started using. Their susceptibility is still a lifetime thing. **Dr. Amen et al. now recommending use of brain imaging throughout treatment to monitor progress in recovery treatment: Amen, DG, Willeumier, K, and Johnson, R. (2012). The clinical utility of brain SPECT imaging in process addictions. J. of Psychoactive Drugs 44(1):18-26, January-March 2012.

Volkow et al J of Neuroscience 2001, Left are images from the striatum level and Right are from the cerebellum level.

From Dr. Raymond Deutch presentation at David E. Smith Addiction Symposium San Francisco June 2014

Dr. Kenneth Blum fMRI studies of heroin addict’s caudate-accumbens regions (purple circle) and the putamen region (pink circle) treatment response to his Synapta GenX neuronutrient complex with thiamine, Vit. B6 &amp; chromium. Placebo Placebo shows the resting state of the fMRI scan of five protracted abstinent Heroin addicts using a 2 X 2 design experiment. The scan represents the effect of an acute dose of matching placebo on the caudate-accumbens-putamen brain region. Notice in the purple circles that there is no response in terms of activation of the dopamine reward areas of the brain. Also notice in the pink circles a serious and intense abnormality (hyperactivity) of the putamen region. This abnormality has been linked to a lack of dopamine D2 receptors in the NAc due to addiction. In response, putamen compensates by becoming hyperactive. It regulates movement and reinforced learning.Synaptose Active treatment with Synaptose shows the resting state of the fMRI scan of the same design experiment. The scan represents the effect of an acute dose of matching Synaptose on the caudate-accumbens-putamen brain region. Notice in the purple circles that there is a strong activation of the dopamine reward site. Moreover, Synaptose induced a &amp;quot;normalization&amp;quot; of the putamen region-pink circles. It is hypothesized that Synaptose caused dopaminergic agonistic activation of dopamine D2 receptors promoting enhanced reward and normalization. These results are still in progress. First report in literature: Brys, Shannon (2013), ‘Test to provide a window into the brain of millions’, Addiction Professional. http://www.addictionpro.com/article/test-provide-window-brain-millionsposted 2/6/13 accessed 2/15/13di

Economic daily UAs maybe to collect from all clients daily but only randomly select some and dump the rest. Item #8 current development of Professional Recovery Coach modeled after Life Coach movements showing good effectiveness when affordable. Some states credential this activity and specify what they can and can not do. Also know as Peer Recovery Support Professional, Certified Recovery Coach, Sober Companion they are paid from $500 to $2,000 per month. Recovery Coach help make decisions and help clarify/understand/accept the role that addiction has on ones life. They help addicts find ways to help them maintain sobriety or reduce harm from their addiction. They can help identify resources for detox, treatment, harm reduction, social services, family services, local and on-line support groups or help a client create a change plan for recovery. They can ont offer primary treatment for addiction, diagnose addiction or any other mental health or medical condition, not be tied to a specific method or means of recovery. This was Lucy Liu’s role in the TV series Elementary as Dr. Watson.

Relapse with other diseases are opportunities to revisit the treatment to offer new more effective resources. Normalizing slips or slides may help addicts reengage in treatment before a full relapse can occur. It is not meant to excuse or condone relapse. Personal observation that relapse is a greater threat of death than during initial addiction thus like to normalize it more.

In fact, memories are the main driving force in every part of our daily lives.

“Footprints of Memory”, spikes, appendages, pimples?

Medieval (500-1500 ad) towns used 7-8 yo child selected to very carefully observe proceedings of an important event then thrown into a river to imprint the memories of the event in the child’s mind emotionally so that it would last a lifetime. (McGaugh, James L. [2003]. Memory &amp; Emotion: The Making of Lasting Memories. Columbia University Press, New Youk, NY)

They are retained as memory bumps or more precisely as dendritic spines. These protrusions grow when a dendrite is stimulated by a sensory input. If the input is intense, the dendritic spine, and therefore the memory becomes semi-permanent. The more we use it, the more permanent it becomes.

For example, this experiment bathed a nerve cell with estrogen, the main female hormone and then stressed the dendrite just as a big high might. As a result, the memory spines grew faster and bigger. Even adjacent spines grew and created the equivalent of a powerful memory network. When this process is mimicked by use of a psychoactive drug, the reward reinforcement circuit is hijacked.

This panel focuses on important regions of the limbic system that was shown in purple on the previous slide. The nucleus accumbens is the “center of the universe” for experiencing the reinforcing effects of drugs of abuse, and nearly all drugs of abuse activate the nucleus accumbens The neuronal projection from the VTA to the nucleus accumbens and prefrontal cortex comprises a major component of what is knows as the mesolimbic dopamine system. Dopamine-containing neurons in the VTA project to the NAcc and release dopamine there. This process is thought to produce sensations of pleasure and well-being. The VTA also sends projections to the prefrontal cortex, and dopamine release there also contributes to the reinforcing effects of drugs of abuse. The prefrontal cortex also receives input from other limbic brain regions thought to be involved in drug reinforcement, such as the amygdala, hippocampus, and anterior cingulate. The prefrontal cortex sends glutamatergic projections back to the nucleus accumbens. As such, the prefrontal cortex is a region that could integrate information from a variety of brain areas associated with drug reinforcement, and modulate responses of these brain areas to drug administration. It has been discovered that nearly all drugs of abuse increase nucleus accumbens dopamine, and for years, the prevailing hypothesis was that dopamine was the key neurotransmitter subserving the reinforcing effects of all drugs of abuse. In recent years, however, it has become apparent that dopamine is not the only “reward” neurotransmitter, and that other neurotransmitters play key roles. In support of this, destroying the dopaminergic projection from the VTA to the nucleus accumbens does not alter alcohol intake in animals. Clearly, other neurotransmitters are involved. Opioid peptides have also been shown to play an important role in alcohol intake. The arcuate nucleus of the hypothalamus contains opioid peptides which can be released and can bind to receptors in the nucleus accumbens and VTA. As such, opioid peptides are reward neurotransmitters in much the same way that dopamine is. What happens is that when we satisfy basic needs by finding water, food, or companionship, a signal is sent through a system known as “the reward reinforcement pathway,” particularly the nucleus accumbens, also known as the go switch. This go switch tells us three things. It says that what we did was necessary for survival, it says that we should remember what we did to find the food, or water, or other basic need and it tells us to do it again, and again, and again.

The red arrow shows the mesolimbic dopaminergic reward/reinforcement pathway of the brain. The reward system is the part of the CNS most responsible for addiction. Normally, it signals pleasure when some physical need is met. It also responds when certain psychoactive drugs are taken. This surge, caused by psychoactive drugs, reinforces their use and often triggers an intense craving. It also disables the satiation/stop switch in the prefrontal cortex.

Discuss here or maybe better latter with the stop signal test slide. Titanic vs. Lusitania: How People behave in a disaster, Time Science 3/3/10 @ http://www.time.com/time/health/article/0,8599,1969142,00.html from Swiss and Austrian behavioral scientist published in Proceedings of the National Academy of Science Benno Torgler, economic professor of Queensland Univ. of Tech. Brisbane Australia is one of the authors. The Titanic with 2,207 passengers and a mortality rate of 68.7% sank on 4/15/1912 about 3 years before Lusitania (5/7/1915) with 1,949 passengers and a mortality rate of 67.3%. Focus was on Third-Class passengers age 35 or older traveling without children as being most likely to die because: age, less fit, deep enough below deck to get to available lifeboats, and no children meant less motivated to survive and others to let them pass ahead. Death rate of this “reference group (rg)” compared to others. Results: Children under 16 were 31% likelier than reference group (rg) to survive on Titanic but on Lusitania they were 0.7% less likely to survive. Males 16-35 on Titanic had a 6.5% poorer survival rate than rg but a 7.9% better than rg on the Lusitania. Females 16-35 on Titanic 48.3% better survival than rg, Lusitania only10.4% better survival than rg. First Class Passengers were 43.9% more likely than rg to get into a life boat on Titanic and 11.5% less likely than rg on the Lusitania. NY Times 3/1/10 article states Children on Titanic were 14.8% more likely to survive than adults while on Lusitania they were 5.3% less likely to survive than adults. Women on Titanic were 53% more likely to survive than men, on Kusitania 1.1% less likely. Projected Explanation: Titanic sunk over 2 hours and 40 minutes or 160 minutes, Lusitania sank in 18 minutes. Time only for Selfish Rationality of flight response on Lusitania giving edge to strong younger males. On Titanic time was enough for good manners (women, children, elders, and even upper class first) had a chance to assert itself. Thus, before initiating any action to use during a trigger must give your brain time for more rational behavior.

In fact, memories are the main driving force in every part of our daily lives.

Metyrapone given to non-opiate users increase CRF and ACTH but has no effect in heroin addicts whose stress hypersensitivity had already turned off their cortisol. When given to abstinent opiate addicts who were not on methadone maintenance their ACTH levels increased as normies. Opiate addicts on methadone for 3 months or more also had normal increase ACTH response to metyrapone because they were no longer in a constant state of experience opiate withdrawal every 6-8 hours or so thus their stress cycle had normalized. Kreek and Koob (1998). Stress and dysregulation of brain reward pathway. Drug and Alcohol Dependence 51:23-47. Kreek et al. (1984). ACTH, cortisol, and b-endorphin response to metyrapone testing during chronic methadone maintenance treatment in humans. Neuropeptides, 5:277-278. CP-154,526 Pfizer labs blocks the actions of CRF. Heilig M and Koob GF (2007), A key role for corticotrophin-releasing factor in alcohol dependence. Trends Neurosci. 30(8):399-406, Lowery EG, Sparrow AM, Breese GR, Knapp DJ and Thiele TE (2008), The CRF-1 receptor antagonist, CP-154,526, attenuates stress-induced increases in ethanol consumption by BALB/cJ mice. Alchol Clin Cep Res, 32(2):240-248,

Craving: An addict in recovery experiencing a high potential for interrupted abstinence that is demonstrable on a visual analog five point Likert scale as a five. Physical Health e.g. chronic pain, dental problems, etc.

Stroop effect or paradigm (John Ridley Stroop 1935) provides measure of impairment Delayed Discounting impairment also a preadolescent marker of future addiction vulnerability – Walter Mischel when he was at Stanford: 1 marshmallow left out for 4 yos vs. 2 as a reward for not eating it until researcher returned. Years of follow up reward delayers had higher SAT scores, less addiction and less divorce. In 8/2011 paper by BJ Casey of Weill Cornell Medical College reports on 59 of the original marshmallow kids. An adult version of the tests showed that high delayers had more activity in their prefrontal cortex and right inferior frontal gyrus than the poor delayers on f MRI examination. Proceedings of the Nat. Acad. Of Science (Aug. 2011)

Now see impact on addiction pathway, cognition, allostasis, craving, relapse potential and even severity and reality of pain

These are PET scans of a person’s brain on cocaine. The yellow areas are where cocaine is exciting the brain, giving a rush. At 6 to 8 minutes there is maximum involvement in all areas and then it starts to diminish. At 20 to 30 minutes, it has spent its major effects. This progression is similar to the effect the anticipation to gamble has on the brain of a gambler. In that case, two forms of adrenaline and dopamine are released, and it takes 20 to 30 minutes for that adrenaline to be reabsorbed. This means that when a craving pops into our head, we need to do something to let 20 to 30 minutes pass to let the adrenaline be reabsorbed. There dozens of activities that we can use . . . .

One thing the scans show is that the more drug used, the more alcohol drunk, the more bets made, especially over a period of time, the greater the shutdown of the brain. The brain of a young heavy drinkers shows almost a complete shutdown of most activity. Alcohol is a depressant. Even with other addictions, the disruption of the brain is obvious.

SPECT, or “single photon emission computerized tomography,” is an imaging technique showing areas of activity and inactivity in the brain. The “holes” are actually areas that are inactivated by the use of a drug or the practice of some behavior. Abstinence restores much, but not all, of the brain function. The more chronic the use, the less the restoration of activity. Methamphetamine is more toxic than heroin or cocaine. Image courtesy of Daniel Amen, M.D.

Because alcohol is a protoplasmic poison, much of the inactivation in the brain of a chronic alcoholic can be long lasting, or permanent. Heroin is less toxic to brain cells, so abstinence restores more brain function. Image courtesy of Daniel Amen, M.D.

SPECT, or “single photon emission computerized tomography,” is an imaging technique showing areas of activity and inactivity in the brain. The “holes” are actually areas that are inactivated by the use of a drug or the practice of some behavior. Abstinence restores much, but not all, of the brain function. The more chronic the use, the less the restoration of activity. Methamphetamine is more toxic than heroin or cocaine. Image courtesy of Daniel Amen, M.D.

Contacts between neurons Cadherin complexes are known to play diverse roles in a cell type-specific manner. In an ongoing study of cadherin-catenin function in interneuronal junctions, Takeichi&amp;apos;s lab has found that αN-catenin, a form of α-catenin specific to the nervous system, is essential to the stabilization of dendritic spines. These projections are important for establishing and maintaining contacts between axons and dendrites, the two principal types of extensions from the neuronal cell body. Previous work showed that cadherins help to regulate the adhesion of dendritic spines to axons, which is a crucial step in synapse formation, a finding which was complemented by this year&amp;apos;s elucidation of αN-catenin&amp;apos;s role. The functional loss of this molecule resulted in dramatic increases in spine motility and shape alterations, while αN-catenin overexpression caused spines, which normally extend and retract intermittently, to turn over at a much lower rate, resulting in abnormal accumulations of mature spines over time. Taken together, these results suggest that αN-catenin is a critical agent in maintaining the appropriate balance between stability and turnover in synaptic contacts. Multipolar, unipolar, bipolar Group Director Masatoshi Takeichi http://www.cdb.riken.go.jp/jp/04_news/annual_reports/2003/WebHelp/Takeichi_Lab.htm Tanabe K, Takeichi M, and Nakagawa S. Identification of a nonchordate-type classic cadherin in vertebrates: Chicken Hz cadherin is expressed in horizontal cells of the neural retina and contains a nonchordate-specific domain complex. Dev Dyn (2004). Abe K, Chisaka O, van Roy F, and Takeichi M. Stability of dendritic spines and synaptic contacts is controlled by αN-catenin. Nat Neurosci (2004). S Nakagawa, S Takada, R Takada and M Takeichi. Identification of the Laminar-Inducing Factor: Wnt-Signal from the Anterior Rim Induces Correct Laminar Formation of the Neural Retina in Vitro. Dev Biol 260:414-25 (2003). Kubo F, Takeichi M and Nakagawa S. Wnt2b controls retinal cell differentiation at the ciliary marginal zone. Development 130:587-98 (2003). Nakagawa S, Takada S, Takada R and Takeichi M. Identification of the laminar-inducing factor: Wnt-signal from the anterior rim induces correct laminar formation of the neural retina in vitro. Dev Biol 260:414-25 (2003). Togashi H, Abe K, Mizoguchi A, Takaoka K, Chisaka O and Takeichi M. Cadherin regulates dendritic spine morphogenesis. Neuron 35:77-89 (2002).

With 100 billion nerve cells and some quadrillion synapses, the brain’s complexity is unparalled. Messages travel in multiple directions with purpose, enabling the senses to transmit messages to the brain that, in turn, send commands back to the appropriate muscles, tissues, and organs. A single nerve cell can receive signals from hundreds, or thousands, of other nerve cells.

http://www.northland.cc.mn.us/biology/AP2Online/Nervous/nerve4.htm

Message transmission occurs when the incoming electrical signal (1) forces the release of neurotransmitters (2) from the vesicles (3) and sends them across the synaptic gap (4) where they will slot into receptor sites (5). which cause an ion molecular gate (6) to open, allowing sodium (7), potassium, or chloride ionic electrical charges in or out. When the total voltage reaches 40–60 mv (millivolts), it fires the signal (8). Neurotransmitters are then released and reabsorbed by reuptake ports [9]) and returned to the vesicles, ready to fire again.

Or almost – any substance that when injected into a rat brain produces a scientific paper!

More than 100 neurotransmitters have been discovered. The most well known are endorphins, dopamine, serotonin, and GABA. Psychoactive drugs can mimic these neurotransmitters. That is why these drugs affect us. Behaviors such as gambling and sexual activity can also activate these neurotransmitters. Types: amino acid (glutamate, GABA), peptides (endorphins, enkephalins), monoamine (dopamine, NorEpi, Epi, histamine, serotonin), Misc. (acetylcholine, anandamide, nitric oxide, adenosine)

In terms of the reward/reinforcement center, dopamine is the most important neurotransmitter. It is sometimes called the reward neurotransmitter. It is dopamine which activates the nucleus accumbens, the go switch. It is also dopamine which also disrupts the stop switch.

Drs. Jennifer Mitchell &amp; Howard Field UCSF’s Gallo Institute Endorphin Study 1/12/12 fMRI show those prone to alcoholism release more endorphin in both the limbic system and the pre frontal cortex.

Also Takahashi, Hidehiko of Kyoto University (2/2012) links pathologic gambling with lower level of norepinephrine transporters in reward/reinforcement circuit of limbic system. This results in greater amount of norepinephrine there that leads them to be less aroused by losses and less sensitive to the pain of losing money. Research done by PET scans.

2011 new AMA definition of Addiction = Reward Deficiency Disorder.

These are actual scans of the density of dopamine receptors in the brains of normal people versus those who are dependent on some psychoactive drug or compulsive behavior. Notice that all addictions show a reduction in the number of receptor sites and therefore an increased need for excess dopamine and therefore an increased craving for extra amounts of the drug to release sufficient dopamine to create the desired feeling.

But we don’t have to be hungry, angry, lonely, tired, or bored to set those memories and cravings going. If we’ve become compulsive about using, drinking, or gambling, if we’ve crowded our head with those memories many non-threatening stimuli can start the “do it again reward reinforcement circuit going” and activate a craving.

Also ”spikes”, “pimples”, “footprints”, (Shawn’s “appendages”)

olfactory

Craving is caused by the sight, smell, and taste of . . . the drug itself, a using partner, a place where the drug was used, cash, and most any memory of one’s drug using career. (sound bite about a specific sensory trigger)

Just the sight of a place where we drank can activate memories of using.

or the practice of the behavior..

And of course the sight of the drug itself or using paraphernalia can begin to activate our craving circuit.

Cash on hand is another common trigger . . . It’s almost the equivalent of carrying around the actual drug.

These PET scans of an addicts brain show the emotional center (amygdala, a part of the old brain) while watching nature videos, and videos of cocaine use. No excitement was generated by the nature video, but the cocaine video did create excitement (a lit-up amygdala signifies excitation). In other scans, the prefrontal cortex became dormant, making the user unable to temper the excitement of the amygdala. Image courtesy Anna Rose Childress, Ph.D.

In fact, memories are the main driving force in every part of our daily lives.

Medieval (500-1500 ad) towns used 7-8 yo child selected to very carefully observe proceedings of an important event then thrown into a river to imprint the memories of the event in the child’s mind emotionally so that it would last a lifetime. (McGaugh, James L. [2003]. Memory &amp; Emotion: The Making of Lasting Memories. Columbia University Press, New Youk, NY)

They are retained as memory bumps or more precisely as dendritic spines. These protrusions grow when a dendrite is stimulated by a sensory input. If the input is intense, the dendritic spine, and therefore the memory becomes semi-permanent. The more we use it, the more permanent it becomes.

For example, this experiment bathed a nerve cell with estrogen, the main female hormone and then stressed the dendrite just as a big high might. As a result, the memory spines grew faster and bigger. Even adjacent spines grew and created the equivalent of a powerful memory network. When this process is mimicked by use of a psychoactive drug, the reward reinforcement circuit is hijacked.

The red arrow shows the mesolimbic dopaminergic reward/reinforcement pathway of the brain. The reward system is the part of the CNS most responsible for addiction. Normally, it signals pleasure when some physical need is met. It also responds when certain psychoactive drugs are taken. This surge, caused by psychoactive drugs, reinforces their use and often triggers an intense craving. It also disables the satiation/stop switch in the prefrontal cortex.

This panel focuses on important regions of the limbic system that was shown in purple on the previous slide. The nucleus accumbens is the “center of the universe” for experiencing the reinforcing effects of drugs of abuse, and nearly all drugs of abuse activate the nucleus accumbens The neuronal projection from the VTA to the nucleus accumbens and prefrontal cortex comprises a major component of what is knows as the mesolimbic dopamine system. Dopamine-containing neurons in the VTA project to the NAcc and release dopamine there. This process is thought to produce sensations of pleasure and well-being. The VTA also sends projections to the prefrontal cortex, and dopamine release there also contributes to the reinforcing effects of drugs of abuse. The prefrontal cortex also receives input from other limbic brain regions thought to be involved in drug reinforcement, such as the amygdala, hippocampus, and anterior cingulate. The prefrontal cortex sends glutamatergic projections back to the nucleus accumbens. As such, the prefrontal cortex is a region that could integrate information from a variety of brain areas associated with drug reinforcement, and modulate responses of these brain areas to drug administration. It has been discovered that nearly all drugs of abuse increase nucleus accumbens dopamine, and for years, the prevailing hypothesis was that dopamine was the key neurotransmitter subserving the reinforcing effects of all drugs of abuse. In recent years, however, it has become apparent that dopamine is not the only “reward” neurotransmitter, and that other neurotransmitters play key roles. In support of this, destroying the dopaminergic projection from the VTA to the nucleus accumbens does not alter alcohol intake in animals. Clearly, other neurotransmitters are involved. Opioid peptides have also been shown to play an important role in alcohol intake. The arcuate nucleus of the hypothalamus contains opioid peptides which can be released and can bind to receptors in the nucleus accumbens and VTA. As such, opioid peptides are reward neurotransmitters in much the same way that dopamine is. Drs. Jennifer Mitchell &amp; Howard Field UCSF’s Gallo Institute Endorphin Study 1/12/12 fMRI show those prone to alcoholism release more endorphin in both the limbic system and the pre frontal cortex.

These PET scans of an addicts brain show the emotional center (amygdala, a part of the old brain) while watching nature videos, and videos of cocaine use. No excitement was generated by the nature video, but the cocaine video did create excitement (a lit-up amygdala signifies excitation). In other scans, the prefrontal cortex became dormant, making the user unable to temper the excitement of the amygdala. Image courtesy Anna Rose Childress, Ph.D.

Imaging studies of the brains of recently abstinent meth abusers, by Edythe London at UCLA, show neurochemical changes that help explain the relapse potential of methamphetamine users. Specifically, the amygdala, the emotional center of the brain, is highly activated (red area) in recently abstinent meth abusers while the prefrontal cortex, the thinking area of the brain that helps control the amygdala, exhibits very low activity (blue area). This means that when craving is triggered in the amygdala, the newly abstinent meth abuser’s ability to control that craving is impaired. Image courtesy of Dr. Edythe London, UCLA Originally done on Cocaine Addicts: Bonson, KB, Grant, SJ, Contoreggi, CS, Links, JM, Metcalfe, J, Weyl, HL, Kurian, V, Ernst, M and London, ED (2002)’ Neural systems and cue-induced cocaine craving. Neuropsychopharmacology 26:376-386.

fMRI study in patients with DSM-IV criteria for alcohol dependence Alcohol abuse can result in altered responsiveness to drug cues that may persist for months or years In this study, subjects took a sip of their preferred alcoholic beverage and viewed images of alcohol-related items. So, there were both gustatory and visual cues. Important to note that the patients are in an alcohol-free state in this study (the sip of alcohol is not enough to produce a pharmacological effect). Several brain regions showed prominent cue-induced activation. Nucleus accumbens and ventral tegmental area are critical components of the reward system The cingulate is part of the prefrontal cortex and is associated with many aspects of executive function – decision making, impulse control, etc. It has a direct connection to the nucleus accumbens. The Insula is thought to mediate higher cognitive processes such as memory and learning related to taste. Becomes activated to other types of drug-related stimuli as well.

Titanic vs. Lusitania: How People behave in a disaster, Time Science 3/3/10 @ http://www.time.com/time/health/article/0,8599,1969142,00.html from Swiss and Austrian behavioral scientist published in Proceedings of the National Academy of Science Benno Torgler, economic professor of Queensland Univ. of Tech. Brisbane Australia is one of the authors. The Titanic with 2,207 passengers and a mortality rate of 68.7% sank about 3 years before Lusitania with 1,949 passengers and a mortality rate of 67.3%. Focus was on Third-Class passengers age 35 or older traveling without children as being most likely to die because: age, less fit, deep enough below deck to get to available lifeboats, and no children meant less motivated to survive and others to let them pass ahead. Death rate of this “reference group (rg)” compared to others. Results: Children under 16 were 31% likelier than reference group (rg) to survive on Titanic but on Lusitania they were 0.7% less likely to survive. Males 16-35 on Titanic had a 6.5% poorer survival rate than rg but a 7.9% better than rg on the Lusitania. Females 16-35 on Titanic 48.3% better survival than rg, Lusitania only10.4% better survival than rg. First Class Passengers were 43.9% more likely than rg to get into a life boat on Titanic and 11.5% less likely than rg on the Lusitania. NY Times 3/1/10 article states Children on Titanic were 14.8% more likely to survive than adults while on Lusitania they were 5.3% less likely to survive than adults. Women on Titanic were 53% more likely to survive than men, on Kusitania 1.1% less likely. Projected Explanation: Titanic sunk over 2 hours and 40 minutes or 160 minutes, Lusitania sank in 18 minutes. Time only for Selfish Rationality of flight response on Lusitania giving edge to strong younger males. On Titanic time was enough for good manners (women, children, elders, and even upper class first) had a chance to assert itself. Thus, before initiating any action to use during a trigger must give your brain time for more rational behavior.

What this means is that first, we must avoid reinforcing existing memories and creating new ones. Continuous abstinence is necessary.

There are dozens of activities one can use to let the time pass to diminish the craving and deactivate the addiction memories. There is exercise . . . Brad P5: “I run and I run almost everyday and not very far, just a couple of miles, just enough to, you know, get a little endorphin release and it makes a really big difference in my life.”

Phone calls to a friend, an AA or NA sponsor, or another fellow AA/NA, GA, or SOS member is a powerful tool . . .Tad: “Well picking up that two ton telephone is one of the hardest things forus to do. I know that when I came into the fellowship, one of the hardest things for me to say was, ‘I need help.”

Brainspotting is ~ combination of Bilateral Sound EMDR, Somatics,and mindfulness meditation. Created by David Grand: Identify a somatic cause of stress or craving and then extiguish it by down regulating the amygdala via identifying an eye position related to the energetic/emotional activation of trauma. Laughter Yoga in Positive Psychology activates oxytocin and endorphin via greet and laugh or other exercise to laugh and smile. Asian Greet and several dozen exercises on the web Brigham Young is said to have kicked snuff by paradoxical intervention mid 1840s, Copenhagen released 1822

Potenza, Marc et al. (Jan. 2012), Addicts’ carvings have different roots in men and women. American Journal of Psychiatry January 31. Yale U. Suggests therefore that women would benefit more from stress-reduction therapies whereas men would benefit more from CBT and 12-Step AA oriented programs Sacks, David (May 2012), Top 5 reasons why women relapse. Psych Central http://blogs.psychcentral.com/addiction-recovery/2012/05/top-5-reasons-women-relapse/#more-315 accessed 5/20/12 Suggest that women like men have major interpersonal, environmental trigger influences but his paper based on observational and anecdotal reports where as the Yale Study was based on brain scans.

Dr. John Hart Slide: From research described in the previous slide, it was discovered that drugs of abuse produce many of their abuse-related effects by activating the limbic system (shown in purple). This region is also responsive to natural rewards such as food, water, and sexual activity. In this simplified depiction, the brain is broadly divided into 2 areas – the outer cortex that is responsible for higher order thinking, executive functioning, and decision making AND the deeper regions of the limbic system that deal with primitive drives and emotions. All mammals and many lower order animals have a limbic system that is essential for survival and for experiencing the reinforcing effects of natural rewards such as food and water, but few mammals have a well-developed cortex psychosocial interventions have utility in altering pathological decision making in drug dependent individuals, but these interventions don’t address the underlying neurobiological changes in the limbic system that are responsible for craving and uncontrollable drug use. The combination of pharmacotherapies and psychosocial interventions afford a two-pronged approach to treating addiction.

Cue-induced reinstatement of ethanol-seeking. During a phase of conditioning rats acquire stable lever pressing for ethanol in the presence of a distinct set of cues. After extinction, the animals are again exposed to the respective cues, formerly associated with ethanol, leading to renewed responding on the ethanol lever in the absence of the primary reinforcer (CTRL). Treatment with naltrexone (NAL; 0.25 mg/kg) or acamprosate (AC; 200 mg/kg) leads to a significant reduction of ethanol-seeking behavior. (Katner et al. (1999) Neuropsychopharmacology 20: 471-479; Bachteler et al. (2005) Neuropsychopharmacology; in press). (B) Reinstatement paradigm. Each lever press is followed by a 25-30 l drop of ethanol as primary reinforcer.

Metyrapone given to non-opiate users increase CRF and ACTH but has no effect in heroin addicts whose stress hypersensitivity had already turned off their cortisol. When given to abstinent opiate addicts who were not on methadone maintenance their ACTH levels increased as normies. Opiate addicts on methadone for 3 months or more also had normal increase ACTH response to metyrapone because they were no longer in a constant state of experience opiate withdrawal every 6-8 hours or so thus their stress cycle had normalized. Kreek and Koob (1998). Stress and dysregulation of brain reward pathway. Drug and Alcohol Dependence 51:23-47. Kreek et al. (1984). ACTH, cortisol, and b-endorphin response to metyrapone testing during chronic methadone maintenance treatment in humans. Neuropeptides, 5:277-278. CP-154,526 Pfizer labs blocks the actions of CRF. Heilig M and Koob GF (2007), A key role for corticotrophin-releasing factor in alcohol dependence. Trends Neurosci. 30(8):399-406, Lowery EG, Sparrow AM, Breese GR, Knapp DJ and Thiele TE (2008), The CRF-1 receptor antagonist, CP-154,526, attenuates stress-induced increases in ethanol consumption by BALB/cJ mice. Alchol Clin Cep Res, 32(2):240-248,

3/6/13 Research pinpoints neural crux of stress induced relapse in rats = in the VTA: GABA-releasing neurons, dopamine-releasing neurons and kappa opioid receptors that affect their connections. Normally GABA puts the brakes on dopamine release and glutamate increases it. GABA does this by forging and strengthening dopamine synapses by a process called long-term potentiation (LTP). Stress interrupts the LTP process hindering GABA’s ability to put the brakes on dopamine release. Stress activates kappa opiate receptors in the VTA but Norbinaltorphimine (nor-BNI), an opioid antagonist, blocks those receptors thereby allowing the LTP process to activate normally and release GABA to put the brakes on dopamine release. Rats treated with nor-BNI and subjected to stress did not relapse whereas untreated rats all relapsed. Graziane, Nicholas; Kauer, Julie; Polter, Abigail – all of Brown, U. and Briand, Lisa; Pierce, Christopher – of U of Penn (2013), Research pinpoints, prevents stress-induced drug relapse in rats. Neuron, March 6, 2013

Actually a sign that brain chemistry is gradually fighting to get back to its normal homeostasis. Treatment has included CBT clinically (Grounding Exercises) and use of acamprosate (aldohol PAWS), carbamazepine (Tegretol), and trazodone

Treatment has included CBT clinically (Grounding Exercises) and use of acamprosate (aldohol PAWS), carbamazepine (Tegretol), and trazodone

Addiction or Drug Induced is non-legally defensible but I think it occurs especially now with “bath Salts” designer stimulants also 2014 research with marijuana and Synthetic cannabinoids associate macro and micro brain structure changes (decreased gray matter and increased ventricular volume) with use by youths that are associated with schizophrenia and have persisted for 2 years of study

Addiction or Drug Induced is non-legally defensible but I think it occurs especially now with “bath Salts” designer stimulants

An increased awareness of the availability of psychoactive drugs and the increased abuse of those substances has made mental health practitioners more aware of the possibility that a client could have a co-occurring disorder. Regular physicians are less aware of these possibilities and more than half incorrectly identify signs and symptoms that indicate a dual diagnosis

The DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders) defines various illnesses caused by the use of drugs. Substance-use disorders are those that lead to abuse and dependence. Substance-induced disorders are physical and mental effects caused directly by the drugs themselves. DSM-5 now uses Substance Related and Addictive Disorders: Mild, Moderate, Severe

Vincent van Gogh self portrait, At Eternity’s Gate,1890. Two months before he shot himself. Absinthe (45-74% ethanol or 90 – 148 proof at his time), Major Depression or a bit of both.

The DSM-IV-TR or the Diagnostic and Statistical Manual of Mental Disorders from the American Psychiatric Association has an extensive classification of mental illnesses. The major divisions are Axis I and Axis II. While many disorders overlap, it is helpful to code mental illnesses for diagnostic and billing purposes. If a client is a user the first diagnosis should be written in disappearing ink because drugs can mimic the symptoms of many psychiatric illnesses.

About 15% of Americans will experience a major depressive disorder during their lifetime; 8.6% do in any one-year period. Criteria for diagnosing depression are feeling and symptoms occurring for most of the day, everyday for a week. Excessive alcohol use, stimulant withdrawal, and the comedown from psychedelics can mimic depression.

Also called manic depression, bipolar disorder is marked by alternating periods of depression, normalcy, and mania. The depression part of the mood swing is extremely severe and can lead to suicidal ideation, attempts, and sometimes death. This disorder often begins in a person’s 20s. Stimulant or psychedelic abuse can often mimic bipolar disorder.

Schizophrenia is a thought disorder. It affects .5 to 1.5% of the population, and there is a strong inherited component to the illness. The effects of several drugs mimic schizophrenia: excess cocaine, amphetamine, ecstasy, and steroid use can cause a toxic psychosis; alcohol abuse depletes nutrients and can cause dementia; withdrawal from downers can be mistaken for a thought disorder. Psychedelics dissociate users from their surroundings and can cause behaviors, mistaken for a thought disorder. (pp. 526–527)

The incidence of mental disorders is consistent in all age groups. If the incidence of substance-related disorders is added, the numbers climb dramatically.

Personality disorders are marked by inflexible behavioral patterns that lead to substantial distress or functional impairment. Anger is intrinsic to personality disorders, as are chronic feelings of unhappiness and alienation from others. These disorders frequently coexist with substance abuse and are especially hard to treat.

Adjustment Disorder in Cancer diagnosis is 40% ap = annual prevalence

Genetic susceptibility to schizophrenia is high. The incidence of shared genes varies from 25% for second-degree relatives such as a niece, to a parent sharing 50% of their genes, to an identical twin who shares 100% of their genes. However, the incidence of schizophrenia in the identical twin of a schizophrenic is only 50%, indicating that a person’s environment and drug use influences susceptibility.

2014 studies show these changes occur with early heavy marijuana use by youths.

The incidence of mood disorders in relatives of those with depression or bipolar disorders is high. For example, the risk of developing depression for a first degree relative of someone with that mood disorder is 15%.

There has been conflict between the mental health community and the substance-abuse treatment community for decades. Recently there has been more cooperation, theoretically enabling a client to enter through any door (MH or SA) and get the proper treatment for co-occurring disorders. In reality there are not enough facilities that handle co-occurring disorders well.

The mental health community is more formal in its treatment and credentialing, whereas the substance abuse treatment community relies more on traditional approaches, and is reluctant to try medication therapy to reduce craving and limit the chance for relapse.

One of the big differences between these systems is how far the professional staff will let a patient fall before they intervene. Substance Abuse often believes that hitting bottom is the only way to break through denial whereas Mental Health intervenes sooner.

Treatment includes group and individual therapy, but the most common therapy for the mental illness side of co-occurring diagnosis is medication. The problem of impaired cognition is particularly acute because both the mental illness and the psychoactive drug can prevent the client from processing and utilizing all the information he or she is receiving.

Over the years there has been a shift from psychiatric hospitals to community mental health centers. This shift to outpatient treatments is due in part to the use of effective psychiatric medications.

Phamacogenomic development rationale: Psychiatrist Ian Reid of Royal Cornhill Hospital Aberdeen Scotland states only 40% of depressed patients respond to the first antidepressant they are given and 10% to 20% don’t respond to any medication. He used this as really a rationale for ECT. I believe this is true for all neuropsychiatric disorder medication because of individual genetic variation, epigenetics and gene polymorphism that medications matched to a person’s genetic makeup can fix. (Dr. Reid quoted in Zimmer, Carl (2012), The Electric Chair, Discover Magazine, November 2012. Since the 1950s the development and use of psychiatric medications has intensified. For some people, especially those with schizophrenia, they are a lifesaver, allowing them to function almost normally in society. However, many psychiatric medications have side effects, which can interfere with normal living.

Many antidepressants control serotonin, norepinephrine, and dopamine. Serotonin, in particular, is the target of the SSRIs or selective serotonin reuptake inhibitors. They block reabsorption of the serotonin neurotransmitters, increasing their activity at various synapses, counteracting depression. Other neurotransmitters might control serotonin and norepinephrine, just norepinephrine, dopamine and norepinephrine.

Most of the antipsychotic medications work by blocking the dopamine receptors in the brain, thereby inhibiting the effects of the excess dopamine that is often part of the cause of the schizophrenia.

Lithium is the primary drug used to control bipolar disorder. Some antidepressants are used while others help control the side effects of lithium which can be severe. Other drugs such as valproate (Depakene) can be used in addition to or instead of lithium.

When benzodiazepines are prescribed for anxiety for a client with a drug abuse disorder follow up is critical. Even limited use of benzodiazepines can trigger the drug addiction. BuSpar and some SSRIs have been used to control anxiety as a way to avoid reactivating the addiction.

David Linden, Abraham Lincoln quotes again.

Science of Recovery

2.
Current Science of Recovery will consist
of Two Parts
• Part I: Evolving Science of Addiction
and its current impact on wellness
• Part II: Developments in Addiction
Treatment & Relapse
(Recrudescence) Prevention:
Promoting Long-Term Recovery and
wellness

6.
Disease/Disorder
A pathological impairment of health or
a condition of abnormal functioning
associated with specific symptoms and
signs caused by internal or external
factors that result in an expected
(predictable) set of discomforts or
dysfunctions
Organ Defect & Cause Symptoms→ →
(Anomaly, Difference)

32.
Dendritic Memory Spines
• Amygdala process emotional memories,
hippocampus all other memories
• Also known as Bumps, Spikes – I like the term
memory protrusions = less triggering
• 4 to 6 sensory inputs of the same stimulus per
hour results in development of a semi-
permanent memory protrusion
• The more often a memory protrusion is
activated the larger it grows and the more
permanent it becomes

35.
Meso-Limbic Reward-Reinforcement
Circuitry of the MFB
 Phase I – Endogenous/Environmental Cue or memory
triggers the Ventral Tegmental Area to release
dopamine which activates core of Nucleus Accumbens
Septi = anticipation of use ON A MISSION! If initiated
difficult to stop
 Phase II – Cues or actual use of addictive drug activates
dopamine “go” switches of lateral hypothalamus and
Nucleus Accumbens (core and shell): COMPULSION FOR
MORE!
 Phase III – Control circuitry of the prefrontal cortex is
inactivated, while the cingulate (bonding) is activated:
results in LOSS OF CONTROL, CONTINUE DESPITE
NEGATIVE CONSEQUENCES

48.
• is a primary, chronic disease of brain reward,
motivation, memory and related circuitry.
Dysfunction in these circuits leads to
characteristic biological, psychological, social
and spiritual manifestations. This is reflected
in an individual pathologically pursuing reward
and/or relief by substance use and other
behaviors.
– (ASAM definition, Short Version)
ADDICTION DEFINITON
American Society of
Addiction Medicine

90.
Part I Science of Addiction
Conclusion
• Addiction is not about morals, will power or
character. It’s about anomalous neurocellular,
neurochemical and neurofunctional features of
vulnerable brains that hijacks their reward and
control circuits resulting in behaviors that are
defined as Addiction – an impairment of choice
• Good news is that the brain is resilient, it’s plastic,
it has the ability to bring itself back to healthy
functionality if given the chance to.

107.
New Paradigm of Addiction
Treatment
Addiction is a systemic and family disorder. It
impacts everyone not just the addict.
Studies now document that treatment of
addiction in isolation, without the involved
treatment of families and systems that are part
of an addicts life will result in a more frequent
return to addictive roles and behaviors following
even positive treatment outcomes

109.
Trauma Informed/Focused Care
Trauma Informed Care is an organizational
structure and treatment framework that involves
understanding, recognizing, and responding to
the effects of all types of trauma. Trauma
Informed Care also emphasizes physical,
psychological and emotional safety for both
consumers and providers, and helps survivors
rebuild a sense of control and empowerment.

111.
Maintenance pharmacotherapy, replacement
therapies, chemically assisted detoxification or
recovery; agonist mediated “anti-priming”
treatments, pharmacologic restoration of
neurohomeostasis, addiction vaccines, phar-
macogenomics and genetic treatment “reset-ting”
the addicted brain. Such terms would have been
incomprehensible or even oxy-moronic in the
recovery field just a few short years. Now,
increased understanding, Addiction Equity Act of
2008 and Affordable Health Care Act are rapidly
increasing the “medicalization” of addiction
treatment.

116.
Tobacco Use Ban at Addiction
Treatment Programs
• Late 1980’s Haight Ashbury Substance Abuse
Treatment Programs
• 2008 New York State and then New Jersey
State addiction treatment programs
• Addictions Recovery Center, Medford, Oregon
January 1, 2012
• State of Oregon July 1, 2012.
Client (inc. non-users), Staff, Administration
(outcomes), and even community conflicts

117.
Negative Impact on Treatment
Completions Clark-Hammon & Gregoire (2011)
• Total % of treatment drop-out nearly doubled
from 30% before the ban to 58% after
• Smoking client drop-outs doubled from 20% prior
to 42% after the ban
• Non-Smoking client drop-outs tripled from 7%
prior to 22% after (chaos of enforcement)
• But overall health of those who did complete
treatment should be much improved

119.
Other Considerations
• Increases Client Trauma in an era of
trauma-informed care
• Inflames staff policing and punitive
practices
• Causes clients to go underground and
perpetuates their “criminal” thinking
• Staff and Clients view of rights being
violated
• Overall health benefits great for all but at
what costs?

124.
Centers for Disease Control and
Prevention (CDC) 7/3/12
Steep Rise in Methadone OD deaths in 2000s
Peaked out in 2007 and now falling
Still, methadone currently accounts for almost
1/3 of U.S. Rx medication deaths
In 2011 methadone was only 2% of all pain
prescriptions yet responsible for more than
30% of Rx pain medication deaths

126.
Current Epidemic of Iatrogenic of Rx
Opioid Pain Medication Addiction
and OD Deaths
In 2010 U.S. Prescription Drug Deaths
(primarily opioid pain medications) were
Greater than Auto Accident Deaths!
Methadone represented 30% of these deaths
in 2010 yet only amounted to only 2% of all
pain medications prescribed

131.
June 2012 US Senate Caucus on
International Narcotics Control
• Rx drugs now second most common form of
drug abuse in the U.S.
• Now responsible for most OD deaths, greater
than heroin and cocaine combined
• Violent pharmacy robberies increased 82%
between 2006 and 2011
• NSDUH data indicates 70% or Rx drugs were
supplied by friends or relatives

132.
July 2013 CDC Report: More Rx med
death than car crash death in U.S.
• 1999-2010 Rx Opioid OD death increased 400%, in
women, 265% in men. 18 women deaths every day!
• Rx meds (esp. Oxycontin & Vicodin) comprised 34% of
suicide deaths in women and 8% in men
• >200,000 women ER visits were due to misuse or abuse of
these drugs, ~one every three minutes
• Rx Opioid OD deaths were greater than 4 times as many
cocaine and heroin deaths in women
• Dr. Thomas Frieden, CDC Director now estimates 42
women deaths each day from Rx Opioid ODs

133.
Opioid Pain Medications
(downers)
In 2010 U.S. Prescription Drug Deaths
(primarily opioid pain medications) were
Greater than Auto Accident Deaths!
Methadone represented 30% of these
deaths in 2010 yet only amounted to only
2% of all pain medications prescribed

134.
Some Unethical, Unwise, and
Over-Prescribing of Opioids
Many horror stories and tabloid reports
especially when a public figure is
involved or overdoses (e.g. This dog
X-ray used in a sting to get pain meds)
But, Most diverted opioid and other prescription
drugs are obtained from friends or family
members

135.
Also many horror stories of overzealous
restriction of such medications from
appropriately medical uses – Pseudo
Addictions?
Many states have regulations recognizing
pain to be the Fifth Vital Sign of medical
treatment and recognize the right of
patients to appropriate assessment and
management of pain

136.
Pseudoaddiction
• Operationally defined as aberrant drug-related
behaviors that make patients with chronic pain
look like addicts.
• These behaviors stop if opioid doses are increased
and pain improves. (Weissman and Haddox, 1989)
• This indicates that the aberrant drug-related
behaviors were actually a search for relief
• Little data on the subject – Only a single human
report as of 2014, but evidence in rats

146.
Chronic use of opioids for pain
management: Expanding Concerns
• Hyperalgesia = increasing pain due to PAF
activation of chemokines (i.e. cytokines) release
with opioid treatment of nociceptive pain that
will disappear with healing
• Neuropathic Pain or Hyperpathia = increasing
pain due to peripheral nerve and spinal dorsal
horn sensitization that will persist after the pain
stimulus is healed

157.
MARIJUANA ADDICTION
• 9-10% of users will meet diagnostic criteria
for cannabis use disorder 2013
• Cannabis is the most commonly identified
substance used by those admitted to
substance abuse treatment facilities in 2013
• 335,833 (18.4%) of those treated for addiction
problems in 2010 list marijuana as their
primary drug of choice TEDS, N-SSATS 2012

159.
Cannabis Use Disorder
Diagnostic Criteria DSM-5
1. larger amounts and longer than intended
2. Inability to decrease or control use
3. Excessive time to get, use, and recover
4. Cravings or urge to use
5. Failure to fulfill work, school, home roles
6. Continued despite negative consequences
7. Important activities ceased or reduced
8. Continued in physically hazardous situations

160.
Diagnostic Criteria Continued
9. Continued despite physical/psychological
problems
10. Tolerance: amount needed to get desired↑
effects or decreased effects from same
amount of cannabis consumed
11. Occurrence of withdrawal or use to relieve or
avoid withdrawal
Mild = 2-3 of symptoms of criteria
Moderate = 4-5
Severe = 6 or more

161.
Marijuana Tolerance
• Rapid development to most marijuana
effects
• Some Cross Tolerance to alcohol but not
with other drugs of abuse

162.
Tissue Dependence
• Seen with daily use of 2-3 “joints” over
several weeks (500mg ave. X 15% = 75 mg.
• Classic loss of control, compulsive use,
cravings and continued use despite
development of negative consequences
• Abstinence induces physical withdrawal
syndrome
• Cross Dependence unclear but use often
occurs in combination with nicotine, alcohol
and other addictive substances

163.
Marijuana Withdrawal Syndrome
Symptoms occur within 8 hours of abstinence
but can be delayed up to 72 hours. Usually
peak in severity on day 10 and may last for up
to 45 days or longer.
Symptoms consist of: irritability, anger, anxiety,
restlessness, nightmares/sleep disturbances
(REM rebound), headaches, depressed mood,
craving, decreased appetite, sweating,chills,
pain, mild tremors (“cold dog shakes”)

164.
Cannabis Withdrawal DSM-5
Within ~a week after cessation: 3 or more of
the following after a few months of heavy use:
1.Irritability, anger, or aggression
2.Nervousness or anxiety
3.Sleep difficulties (insomnia, disturbing dreams -
REM rebound from suppression)
4.Decreased appetite or weight loss
5.Restlessness
6.Depressed Mood

169.
Treatment Works!
Kibou is the Japanese Kanji (calligraphy) meaning
hope. It is comprised of Ki = hope and Bou = wish.
Combined it symbolizes a good sign to overcome
difficult situations or failures.
Addiction is one of the most treatable and manageable
of all chronic, persistent medical disorders with
positive treatment outcomes that favorably compare
with the treatment of diabetes, hypertension, asthma,
et al. chronic, persistent illnesses.
Relapse is prevalent in the treatment of all chronic
medical disorders. Relapse rates after addiction
treatment also compare favorably with treatment of
other illnesses.
Kibou

170.
RECOVERY
The Resilient Brain
8-10 Months Rigorous Uninterrupted
Treatment for Reasonable Outcomes
Implies time needed for brain to become
functional
Takes up to 2 years for greater functioning
to return

177.
• Complex but treatable disease affecting brain
function and behavior +/-
• No single treatment is appropriate for all +
• Must be readily available -
• Attends to the multiple needs of individuals ~
• Crucial to remain in treatment for adequate
period of time -
• Individual, group and other evidence-based
behavioral therapies should be employed +
• Medications combined with counseling and
behavioral therapies are important -

178.
• Service plans and treatment to be assessed
continually and modified as needed +
• Evaluate & address mental health and other co-
occurring disorders for best outcomes -
• Medically assisted detox is only a first step and has
little impact on long-term outcomes -
• Treatment does not need to be voluntary to be
effective + (by default)
• Rigorous monitoring throughout treatment for
drug use may help reduce relapses -
• Disease assessment (i.e. HIV, HCV, HBV, TB) and Risk-
Reduction Education a must ~+

184.
Recovery
• Continued Abstinence
• Discovery of Natural Highs
• Recovery of neurotransmitters and
of natural brain functions
• Positive lifestyles and quality of
life enhancements
• Remember: Not an Event but a Process
One does not cure addiction, you treat it and manage it like any
other chronic persistent medical disorder

186.
• Good News!
Recovery Works and the brain is resilient!
• Not so Good News
It takes time, several months to years
to just become functional, and
a bit more to enjoy life again
• Addiction Pathways
Shrink with Disuse and new alternate pathways
become established (“Extinction”) but addicted
neurons are permanent and Recovery is a Life-
Long Process!

187.
Conclusions
◆ Addiction treatment
results in miraculous
outcomes for those
who commit to and
maintain continuous
recovery efforts.
◆ Developments in treatments of
addiction continues to improve outcomes
that improve lives and health for all.
Me at Series End

188.
Last Section of Current Science
Recovery
End of this exhausting
Journey is in sight

191.
Slip and Relapse
Slip = momentary, short-lived, isolated and
limited use of addictive substance or
practice of compulsive behaviors after a
period of abstinence (Slide?)
Relapse = return to persistent and
compulsive drug use or behavioral practice
after a period of abstinence
The frequency that a single use of drug or
addictive behavior (Slip) results in a Relapse
of a recovering addict is 95%

197.
Dendritic Memory Spines
• Amygdala process emotional memories,
hippocampus all other memories
• Also known as Bumps, Spikes – I like the term
memory protrusions = less triggering
• 4 to 6 sensory inputs of the same stimulus per
hour results in development of a semi-
permanent memory protrusion
• The more often a memory protrusion is
activated the larger it grows and the more
permanent it becomes

225.
ENDOGENOUS CRAVING
Analogous to diabetes, hypothyroidism, et. al.,
an allostasis develops with continued use of an
addictive substance. When abstinence is initiated,
the brain craves the substance in an effort to
maintain its imbalanced state through a variety of
mechanisms: amygdala via emotional memories,
attachment and bonding via the cingulate gyrus
facilitated by delta fosB transcriptase and hypo-
functioning of PFC CK Himmelsbach1941, Inaba & Cohen
1986, Fredrick Von Stieff 2011

231.
Psychoactive Drugs Affect
Perception, Mood, and States of
Consciousness by mimicking or
Disrupting the Natural Chemistry of
the Brain
Expanded Definition = Any Behaviors (e.g.
Gambling) that Alter Moods and Affect the
Brain’s Addiction Circuitries and Pathways

249.
Craving can be causedCraving can be caused
by the sight, smell,by the sight, smell,
and taste ofand taste of
** a using partnera using partner
* a using place* a using place
* a dealer* a dealer
* cash* cash
* the drug itself* the drug itself

250.
MEMORIES
Both Endogenous &
Environmental Triggers
activate memory pathways
where neurons search for the
most convenient way it resolved
the issues or needs in the past:
USE DRUGS!

254.
Dendritic Memory Spines
• Amygdala process emotional memories,
hippocampus all other memories
• Also known as Bumps, Spikes – I like the term
memory protrusions = less triggering
• 4 to 6 sensory inputs of the same stimulus per
hour results in development of a semi-
permanent memory protrusion
• The more often a memory protrusion is
activated the larger it grows and the more
permanent it becomes

284.
Definition
The existence in an individual of
at least one major mental health
disorder along with an alcohol or
drug use disorder
SAMHSA 2002; NIMH 1999

285.
Incidence
• 44% of alcoholics and 64.4% substance
abusers admitted for treatment in 1990 had at
least one major mental illness
• Conversely 29-34% of all mentally ill patients
admitted for treatment in 1990 also had an
alcohol or drug use disorders.
Regier et al. 1990
• Note:Studies vary widely depending on the
populations studied

299.
● Need for “Rule-Out” careful diagnosis: Substance
Induced vs. Pre-Existing
Best Outcomes when both disorders treated at●
the same time in one treatment system
Same neurochemical imbalances involved with●
both disorders
Major MH disorders: Thought, Affective, Mood,●
Anxiety, and Personality

300.
Four Quadrant Model: A Treatment
Guide? Kenneth Minkoff, M.D.
Quadrant 4
More Severe Mental
Disorder with
More Severe Substance
Use Disorder
Quadrant 3
Less Severe Mental
Disorder with
More Severe Substance
Use Disorder
Quadrant 1
Less Severe Mental
Disorder with
Less Severe Substance Use
Disorder
Quadrant 2
More Severe Mental
Disorder with
Less Severe Substance Use
Disorder

301.
Note: Only 40% respond
positively to the first
medication used to treat
their mental health disorder

302.
Key to Effective Mental Health
Treatment Outcomes
1. COMPLIANCE with medication dosage and
frequency as prescribed by their psychiatric
care provider
2. COMMUNICATION, active and continually
about medication and emotional feelings
with their mental health clinician or therapist

304.
Conclusion
Hope! Though the challenges
to maintaining sobriety are
daunting, developments in
treatment continue to improve
outcomes. Remember, the
qualities in those that makes
one vulnerable to addiction are
also qualities we look for in our
charismatic leaders.
Questions?

305.
Recovery
• Continued Abstinence
• Discovery of Natural Highs
• Recovery of neurotransmitters and
of natural brain functions
• Positive lifestyles and quality of
life enhancements
• Remember: Not an Event but a Process
One does not cure addiction, you treat it and manage it like any
other chronic persistent medical disorder

306.
Seminar on Neuroscience of Addiction and
Recovery is Completed
Great Work All and Thank You All for Attending